{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:49:26Z","timestamp":1782197366350,"version":"3.54.5"},"reference-count":218,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acquired resistance\u2014including immune exclusion, myeloid-dominant suppression, and genotype-driven \u201ccold\u201d tumor states. In this review, we synthesize emerging insights into the immune landscape of CCA, integrating data from single-cell, spatial, and translational studies to define the cellular and molecular circuits governing immune evasion. Beyond canonical biomarkers such as mismatch repair and microsatellite status, we highlight how spatial organization of immunity\u2014in particular, tertiary lymphoid structures, dynamic myeloid and stromal interactions, and pathway-level features\u2014shape immunotherapy responsiveness. We also examine how tumor-intrinsic alterations, including IDH1 mutation, FGFR2 fusions, KRAS activation, and MTAP loss, define distinct immunologic phenotypes with direct implications for immunotherapeutic response and biomarker-driven patient selection. We evaluate the expanding clinical trial landscape of immunotherapy in CCA and more broadly in BTC, including adoptive cell therapies and cancer vaccines. Together, these advances position CCA as a paradigm of how tumor genotype and microenvironment co-evolve to define immunotherapy sensitivity and resistance.<\/jats:p>","DOI":"10.3390\/cancers18122001","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"2001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Emanuelle","family":"Rizk","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2896-4570","authenticated-orcid":false,"given":"Patrick","family":"Foley","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soravis","family":"Osataphan","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41575-025-01153-w","article-title":"Cholangiocarcinoma 2026: Status Quo, Unmet Needs and Priorities","volume":"23","author":"Banales","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","first-page":"101171","article-title":"Mapping the Landscape of Biliary Tract Cancer in Europe: Challenges and Controversies","volume":"50","author":"Rimassa","year":"2025","journal-title":"Lancet Reg. Health\u2013Eur."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/oncolo\/oyac150","article-title":"Temporal Changes in Cholangiocarcinoma Incidence and Mortality in the United States from 2001 to 2017","volume":"27","author":"Javle","year":"2022","journal-title":"Oncologist"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.jhep.2019.07.024","article-title":"Global Trends in Mortality from Intrahepatic and Extrahepatic Cholangiocarcinoma","volume":"71","author":"Khan","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jhbp.62","article-title":"Roles of Liver Fluke Infection as Risk Factor for Cholangiocarcinoma","volume":"21","author":"Sithithaworn","year":"2014","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41575-022-00741-4","article-title":"Immunology and Immunotherapy of Cholangiocarcinoma","volume":"20","author":"Greten","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.jhep.2023.05.010","article-title":"Immunobiology of Cholangiocarcinoma","volume":"79","author":"Tomlinson","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/COC.0000000000001258","article-title":"Demographic and Regional Trends in Mortality Related to Cholangiocarcinoma in the United States: 1999 to 2020","volume":"49","author":"Jamil","year":"2026","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/sj.bjc.6605211","article-title":"Gemcitabine Alone or in Combination with Cisplatin in Patients with Advanced or Metastatic Cholangiocarcinomas or Other Biliary Tract Tumours: A Multicentre Randomised Phase II Study\u2014The UK ABC-01 Study","volume":"101","author":"Valle","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer","volume":"362","author":"Valle","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"EVIDoa2200015","DOI":"10.1056\/EVIDoa2200015","article-title":"Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer","volume":"1","author":"Oh","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","article-title":"Pembrolizumab in Combination with Gemcitabine and Cisplatin Compared with Gemcitabine and Cisplatin Alone for Patients with Advanced Biliary Tract Cancer (KEYNOTE-966): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial","volume":"401","author":"Kelley","year":"2023","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.jhep.2025.05.003","article-title":"Durvalumab plus Chemotherapy in Advanced Biliary Tract Cancer: 3-Year Overall Survival Update from the Phase III TOPAZ-1 Study","volume":"83","author":"Oh","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","article-title":"Durvalumab or Placebo plus Gemcitabine and Cisplatin in Participants with Advanced Biliary Tract Cancer (TOPAZ-1): Updated Overall Survival from a Randomised Phase 3 Study","volume":"9","author":"Oh","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/hep.31092","article-title":"Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma","volume":"72","author":"Job","year":"2020","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1158\/1078-0432.CCR-21-1157","article-title":"Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma","volume":"28","author":"Chen","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1158\/2159-8290.CD-21-1640","article-title":"Geospatial Immune Heterogeneity Reflects the Diverse Tumor\u2013Immune Interactions in Intrahepatic Cholangiocarcinoma","volume":"12","author":"Lin","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41467-024-44748-8","article-title":"A Transcriptome Based Molecular Classification Scheme for Cholangiocarcinoma and Subtype-Derived Prognostic Biomarker","volume":"15","author":"Fan","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1136\/gutjnl-2021-326514","article-title":"Novel Microenvironment-Based Classification of Intrahepatic Cholangiocarcinoma with Therapeutic Implications","volume":"72","author":"Kepecs","year":"2023","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jhep.2020.03.008","article-title":"Molecular Classification and Therapeutic Targets in Extrahepatic Cholangiocarcinoma","volume":"73","author":"Montal","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1053\/j.gastro.2013.01.001","article-title":"Integrative Molecular Analysis of Intrahepatic Cholangiocarcinoma Reveals 2 Classes That Have Different Outcomes","volume":"144","author":"Sia","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ccell.2021.12.006","article-title":"Proteogenomic Characterization Identifies Clinically Relevant Subgroups of Intrahepatic Cholangiocarcinoma","volume":"40","author":"Dong","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/hep.32624","article-title":"Proteogenomic Characterization of Cholangiocarcinoma","volume":"77","author":"Deng","year":"2023","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2100510","DOI":"10.1200\/PO.21.00510","article-title":"Clinical, Genomic, and Transcriptomic Data Profiling of Biliary Tract Cancer Reveals Subtype-Specific Immune Signatures","volume":"6","author":"Mody","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1158\/2159-8290.CD-17-0368","article-title":"Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma","volume":"7","author":"Jusakul","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1136\/gutjnl-2023-330483","article-title":"Integrative Multiomics Enhancer Activity Profiling Identifies Therapeutic Vulnerabilities in Cholangiocarcinoma of Different Etiologies","volume":"73","author":"Hong","year":"2024","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1158\/1078-0432.CCR-25-1834","article-title":"Clinicogenomic Characterization of Primary Sclerosing Cholangitis\u2013Associated Biliary Tract Cancers","volume":"32","author":"Wang","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1158\/2159-8290.CD-20-0304","article-title":"Gut Microbiome Directs Hepatocytes to Recruit MDSC and Promote Cholangiocarcinoma","volume":"11","author":"Zhang","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1158\/2159-8290.CD-21-1077","article-title":"Mutant IDH Inhibits IFN\u03b3\u2013TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in Cholangiocarcinoma","volume":"12","author":"Wu","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1097\/HEP.0000000000001185","article-title":"Tumor-Derived CCL2 Drives Tumor Growth and Immunosuppression in IDH1-Mutant Cholangiocarcinoma","volume":"82","author":"Zabransky","year":"2025","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e2300544","DOI":"10.1200\/PO.23.00544","article-title":"Comprehensive Immunogenomic Profiling of IDH1-\/2 -Altered Cholangiocarcinoma","volume":"8","author":"Makawita","year":"2024","journal-title":"JCO Precis. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eadl6173","DOI":"10.1126\/science.adl6173","article-title":"Mutant IDH1 Inhibition Induces dsDNA Sensing to Activate Tumor Immunity","volume":"385","author":"Wu","year":"2024","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1158\/1078-0432.CCR-25-3284","article-title":"MAPK Pathway Mutations Emerge in Mutant IDH1 Inhibitor-Resistant Cholangiocarcinoma and Attenuate the IFN Response","volume":"32","author":"Wan","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e0632","DOI":"10.1097\/HC9.0000000000000632","article-title":"Deep Immune Profiling of Intrahepatic Cholangiocarcinoma with CODEX Multiplexed Imaging","volume":"9","author":"Baretti","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5431","DOI":"10.1158\/1078-0432.CCR-22-1244","article-title":"FGFR mRNA Expression in Cholangiocarcinoma and Its Correlation with FGFR2 Fusion Status and Immune Signatures","volume":"28","author":"Sridharan","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e006303","DOI":"10.1136\/jitc-2022-006303","article-title":"Specific Recognition of an FGFR2 Fusion by Tumor Infiltrating Lymphocytes from a Patient with Metastatic Cholangiocarcinoma","volume":"11","author":"White","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e249840","DOI":"10.1001\/jamanetworkopen.2024.9840","article-title":"KRAS Allelic Variants in Biliary Tract Cancers","volume":"7","author":"Moffat","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oncolo\/oyae011","article-title":"Methylthioadenosine Phosphorylase Genomic Loss in Advanced Gastrointestinal Cancers","volume":"29","author":"Ngoi","year":"2024","journal-title":"Oncologist"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2400842","DOI":"10.1200\/PO-24-00842","article-title":"Prognostic Role of MTAP Loss in Cholangiocarcinoma","volume":"9","author":"Lyon","year":"2025","journal-title":"JCO Precis. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5606","DOI":"10.1038\/s41467-021-25894-9","article-title":"9p21 Loss Confers a Cold Tumor Immune Microenvironment and Primary Resistance to Immune Checkpoint Therapy","volume":"12","author":"Han","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.ccell.2023.09.005","article-title":"Enzyme-Mediated Depletion of Methylthioadenosine Restores T Cell Function in MTAP-Deficient Tumors and Reverses Immunotherapy Resistance","volume":"41","author":"Gjuka","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1136\/gutjnl-2024-332998","article-title":"Identification of PRMT5 as a Therapeutic Target in Cholangiocarcinoma","volume":"74","author":"Elurbide","year":"2024","journal-title":"Gut"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/imm.13587","article-title":"MTAP Deficiency Contributes to Immune Landscape Remodelling and Tumour Evasion","volume":"168","author":"Chang","year":"2023","journal-title":"Immunology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jhep.2020.05.039","article-title":"Single-Cell Transcriptomic Architecture and Intercellular Crosstalk of Human Intrahepatic Cholangiocarcinoma","volume":"73","author":"Zhang","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/HEP.0000000000001283","article-title":"Spatial Single-Cell Proteomics Landscape Decodes the Tumor Microenvironmental Ecosystem of Intrahepatic Cholangiocarcinoma","volume":"83","author":"Hong","year":"2026","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.jhep.2019.05.026","article-title":"Reduction of Immunosuppressive Tumor Microenvironment in Cholangiocarcinoma by Ex Vivo Targeting Immune Checkpoint Molecules","volume":"71","author":"Zhou","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.jhep.2022.05.043","article-title":"Multimodal Single-Cell Profiling of Intrahepatic Cholangiocarcinoma Defines Hyperactivated Tregs as a Potential Therapeutic Target","volume":"77","author":"Alvisi","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5380","DOI":"10.1172\/JCI137110","article-title":"Targeting Tumor-Associated Macrophages and Granulocytic Myeloid-Derived Suppressor Cells Augments PD-1 Blockade in Cholangiocarcinoma","volume":"130","author":"Loeuillard","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wirta, E.-V., Szeto, S., Koppatz, H., Nordin, A., M\u00e4kisalo, H., Arola, J., Sir\u00e9n, J., Ahtiainen, M., B\u00f6hm, J., and Mecklin, J.-P. (2024). High Immune Cell Infiltration Predicts Improved Survival in Cholangiocarcinoma. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1333926"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1186\/s12935-020-01687-w","article-title":"Intrahepatic Cholangiocarcinoma Induced M2-Polarized Tumor-Associated Macrophages Facilitate Tumor Growth and Invasiveness","volume":"20","author":"Yuan","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00595-014-0989-y","article-title":"Macrophage Density and Macrophage Colony-Stimulating Factor Expression Predict the Postoperative Prognosis in Patients with Intrahepatic Cholangiocarcinoma","volume":"45","author":"Oishi","year":"2015","journal-title":"Surg. Today"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s41419-026-08685-2","article-title":"Decoding the CAF\u2013TAM Axis: Multi-Omics Dissection and Therapeutic Targeting of Stromal\u2013Immune Crosstalk in the Tumor Microenvironment","volume":"17","author":"Fu","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1158\/0008-5472.CAN-15-2973","article-title":"FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling","volume":"76","author":"Yang","year":"2016","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1186\/s12967-023-04804-1","article-title":"ALOX5 Acts as a Key Role in Regulating the Immune Microenvironment in Intrahepatic Cholangiocarcinoma, Recruiting Tumor-Associated Macrophages through PI3K Pathway","volume":"21","author":"Chen","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e001946","DOI":"10.1136\/jitc-2020-001946","article-title":"Tumor-Associated Neutrophils and Macrophages Interaction Contributes to Intrahepatic Cholangiocarcinoma Progression by Activating STAT3","volume":"9","author":"Zhou","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41586-022-05400-x","article-title":"Liver Tumour Immune Microenvironment Subtypes and Neutrophil Heterogeneity","volume":"612","author":"Xue","year":"2022","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"104935","DOI":"10.1016\/j.yexmp.2024.104935","article-title":"Facilitating Cholangiocarcinoma Inhibition by Targeting CD47","volume":"140","author":"Vaeteewoottacharn","year":"2024","journal-title":"Exp. Mol. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/hep.32222","article-title":"Mucosal-Associated Invariant T-Cell Tumor Infiltration Predicts Long-Term Survival in Cholangiocarcinoma","volume":"75","author":"Zimmer","year":"2022","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1016\/j.cell.2023.07.026","article-title":"Tumor-Associated Macrophages Trigger MAIT Cell Dysfunction at the HCC Invasive Margin","volume":"186","author":"Ruf","year":"2023","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1158\/1078-0432.CCR-15-0715","article-title":"PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma","volume":"22","author":"Sabbatino","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2035919","DOI":"10.1080\/2162402X.2022.2035919","article-title":"MICA\/B-Targeted Antibody Promotes NK Cell-Driven Tumor Immunity in Patients with Intrahepatic Cholangiocarcinoma","volume":"11","author":"Oliviero","year":"2022","journal-title":"Oncoimmunology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5309","DOI":"10.1016\/j.cell.2021.09.020","article-title":"Hallmarks of Response, Resistance, and Toxicity to Immune Checkpoint Blockade","volume":"184","author":"Morad","year":"2021","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e010173","DOI":"10.1136\/jitc-2024-010173","article-title":"Comparative Impact of Tertiary Lymphoid Structures and Tumor-Infiltrating Lymphocytes in Cholangiocarcinoma","volume":"13","author":"Chung","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41419-025-07388-4","article-title":"TIGIT Expression in Extrahepatic Cholangiocarcinoma and Its Impact on CD8 + T Cell Exhaustion: Implications for Immunotherapy","volume":"16","author":"Tang","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41577-019-0224-6","article-title":"TIM3 Comes of Age as an Inhibitory Receptor","volume":"20","author":"Wolf","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1200\/JCO-25-02487","article-title":"B7-H3 as a Universal Target for Solid Tumor Therapy: Clinical Promise and Biological Complexity","volume":"44","author":"Huang","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.it.2020.12.008","article-title":"VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy","volume":"42","author":"Yuan","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Heij, L., Bednarsch, J., Tan, X., Rosin, M., Appinger, S., Reichel, K., Pecina, D., Doukas, M., van Dam, R.M., and Garcia Vallejo, J. (2023). Expression of Checkpoint Molecules in the Tumor Microenvironment of Intrahepatic Cholangiocarcinoma: Implications for Immune Checkpoint Blockade Therapy. Cells, 12.","DOI":"10.3390\/cells12060851"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Yin, Z., Li, J., Liu, L., Zhang, L., Zhang, W., and Ma, B. (2026). The Expression Status and Clinical Value of TIM-3 in Intrahepatic Cholangiocarcinoma. BMC Cancer.","DOI":"10.1186\/s12885-026-16292-9"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/apm.12837","article-title":"B7-H3 Expression and Its Correlation with Clinicopathologic Features, Angiogenesis, and Prognosis in Intrahepatic Cholangiocarcinoma","volume":"126","author":"Cheng","year":"2018","journal-title":"APMIS"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jhep.2021.10.030","article-title":"Distribution and Density of Tertiary Lymphoid Structures Predict Clinical Outcome in Intrahepatic Cholangiocarcinoma","volume":"76","author":"Ding","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.ccell.2021.03.012","article-title":"Promotion of Cholangiocarcinoma Growth by Diverse Cancer-Associated Fibroblast Subpopulations","volume":"39","author":"Affo","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jhep.2020.11.018","article-title":"TWEAK\/Fn14 Signalling Promotes Cholangiocarcinoma Niche Formation and Progression","volume":"74","author":"Dwyer","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Waki, Y., Morine, Y., Noma, T., Takasu, C., Teraoku, H., Yamada, S., Saito, Y., Ikemoto, T., and Shimada, M. (2023). Association between High Expression of Intratumoral Fibroblast Activation Protein and Survival in Patients with Intrahepatic Cholangiocarcinoma. BMC Gastroenterol., 23.","DOI":"10.1186\/s12876-023-03012-x"},{"key":"ref_75","first-page":"957","article-title":"Alpha-Smooth Muscle Actin-Positive Fibroblasts Promote Biliary Cell Proliferation and Correlate with Poor Survival in Cholangiocarcinoma","volume":"21","author":"Chuaysri","year":"2009","journal-title":"Oncol. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1158\/0008-5472.CAN-12-2130","article-title":"Therapeutic Effects of Deleting Cancer-Associated Fibroblasts in Cholangiocarcinoma","volume":"73","author":"Mertens","year":"2013","journal-title":"Cancer Res."},{"key":"ref_77","unstructured":"(2026, January 06). Research, C. for D.E. and FDA Approves Durvalumab for Locally Advanced or Metastatic Biliary Tract Cancer, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S2468-1253(19)30086-X","article-title":"Nivolumab Alone or in Combination with Cisplatin plus Gemcitabine in Japanese Patients with Unresectable or Recurrent Biliary Tract Cancer: A Non-Randomised, Multicentre, Open-Label, Phase 1 Study","volume":"4","author":"Ueno","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e000367","DOI":"10.1136\/jitc-2019-000367","article-title":"Efficacy and Biomarker Analysis of Nivolumab plus Gemcitabine and Cisplatin in Patients with Unresectable or Metastatic Biliary Tract Cancers: Results from a Phase II Study","volume":"8","author":"Feng","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e70428","DOI":"10.1111\/liv.70428","article-title":"Durvalumab in Advanced Biliary Tract Cancer: Real-World Data From a Large Cohort of Patients Across Multiple International Centers","volume":"45","author":"Rimini","year":"2025","journal-title":"Liver Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"114199","DOI":"10.1016\/j.ejca.2024.114199","article-title":"Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer: A Large Real-Life Worldwide Population","volume":"208","author":"Rimini","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"oyae306","DOI":"10.1093\/oncolo\/oyae306","article-title":"Real-World Effectiveness and Prognostic Factors of Durvalumab plus Chemotherapy in a Multicentric Cohort with Advanced Biliary Tract Cancer","volume":"30","author":"Huang","year":"2025","journal-title":"Oncologist"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"oyae256","DOI":"10.1093\/oncolo\/oyae256","article-title":"Efficacy of Cisplatin-Gemcitabine-Durvalumab in Patients with Advanced Biliary Tract Cancer Experiencing Early vs Late Disease Relapse after Surgery: A Large Real-Life Worldwide Population","volume":"30","author":"Salani","year":"2025","journal-title":"Oncologist"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e2400216","DOI":"10.1200\/GO.24.00216","article-title":"Gemcitabine Cisplatin and Durvalumab Experience in Advanced Biliary Tract Cancers: A Real-World, Multicentric Data From India","volume":"10","author":"Muddu","year":"2024","journal-title":"JCO Glob. Oncol."},{"key":"ref_85","unstructured":"Staff, T.A.P. (2026, January 05). FDA Grants Full Approval to Pembrolizumab for Certain Adult and Pediatric Patients with Advanced MSI-H or dMMR Solid Tumors. Available online: https:\/\/ascopost.com\/news\/march-2023\/fda-grants-full-approval-to-pembrolizumab-for-certain-adult-and-pediatric-patients-with-advanced-msi-h-or-dmmr-solid-tumors\/."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"viii210","DOI":"10.1093\/annonc\/mdy282.009","article-title":"Pembrolizumab for Advanced Biliary Adenocarcinoma: Results from the Multicohort, Phase II KEYNOTE-158 Study","volume":"29","author":"Ueno","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1002\/ijc.33013","article-title":"Efficacy and Safety of Pembrolizumab for the Treatment of Advanced Biliary Cancer: Results from the KEYNOTE-158 and KEYNOTE-028 Studies","volume":"147","author":"Oh","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1001\/jamaoncol.2020.0930","article-title":"A Phase 2 Multi-Institutional Study of Nivolumab for Patients with Advanced Refractory Biliary Tract Cancer","volume":"6","author":"Kim","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/S1470-2045(18)30700-9","article-title":"Nivolumab plus Ipilimumab or Nivolumab Alone versus Ipilimumab Alone in Advanced Melanoma (CheckMate 067): 4-Year Outcomes of a Multicentre, Randomised, Phase 3 Trial","volume":"19","author":"Hodi","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1200\/JCO.2017.76.9901","article-title":"Durable Clinical Benefit with Nivolumab Plus Ipilimumab in DNA Mismatch Repair\u2013Deficient\/Microsatellite Instability\u2013High Metastatic Colorectal Cancer","volume":"36","author":"Overman","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1056\/NEJMoa1712126","article-title":"Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1001\/jamaoncol.2020.2814","article-title":"Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients with Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial","volume":"6","author":"Klein","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1002\/cam4.4593","article-title":"Tolerability and Efficacy of Durvalumab, Either as Monotherapy or in Combination with Tremelimumab, in Patients from Asia with Advanced Biliary Tract, Esophageal, or Head-and-Neck Cancer","volume":"11","author":"Doki","year":"2022","journal-title":"Cancer Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e6912","DOI":"10.1002\/cam4.6912","article-title":"Combined Immune Checkpoint Inhibition with Durvalumab and Tremelimumab with and without Radiofrequency Ablation in Patients with Advanced Biliary Tract Carcinoma","volume":"13","author":"Monge","year":"2024","journal-title":"Cancer Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e008872","DOI":"10.1136\/jitc-2024-008872","article-title":"Randomized, Open-Label, Phase 2 Study of Nivolumab plus Ipilimumab or Nivolumab Monotherapy in Patients with Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden","volume":"12","author":"Schenker","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_96","unstructured":"(2026, January 06). NCCN Clinical Practice Guidelines in Oncology: Biliary Tract Cancers Version 2.2025 2025. Available online: https:\/\/jnccn.org\/view\/journals\/jnccn\/23\/9\/article-p403.xml."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1080\/07357907.2022.2108827","article-title":"Adverse Events Induced by Nivolumab Plus Ipilimumab Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis","volume":"40","author":"Kamat","year":"2022","journal-title":"Cancer Investig."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa2407417","article-title":"Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma","volume":"392","author":"Wolchok","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1200\/JCO.2021.39.3_suppl.321","article-title":"Lenvatinib plus Pembrolizumab for Patients with Previously Treated Biliary Tract Cancers in the Multicohort Phase II LEAP-005 Study","volume":"39","author":"Villanueva","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1158\/2767-9764.CRC-26-0018","article-title":"Lenvatinib Plus Pembrolizumab for Patients with Previously Treated Advanced Gastric, Biliary Tract, or Pancreatic Cancer: Results From the Phase 2 LEAP-005 Study","volume":"6","author":"Rha","year":"2026","journal-title":"Cancer Res. Commun."},{"key":"ref_102","first-page":"CLO25-099","article-title":"CLO25-099: Lenvatinib with Pembrolizumab in Advanced Biliary Tract Cancer","volume":"23","author":"Grewal","year":"2025","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1056\/NEJMoa2513918","article-title":"Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma","volume":"394","author":"Shi","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/S1470-2045(25)00376-6","article-title":"Conversion Therapy of Tislelizumab plus Lenvatinib and GEMOX in Unresectable Locally Advanced Biliary Tract Cancer (ZSAB-TransGOLP): A Multicentre, Prospective, Phase 2 Study","volume":"26","author":"Shi","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Huang, X.-Y., Shi, G.-M., Zheng, Z.-T., Sun, H.-C., Liang, F., Ji, Y., Chen, Y., Yang, G.-H., Hu, Z.-Q., and Lu, J.-C. (2025). Anti-PD1 Antibody Toripalimab Combined with Lenvatinib, or GEMOX Chemotherapy Combined with Lenvatinib as First-Line Therapy in Patients with Advanced Intrahepatic Cholangiocarcinoma: A Randomized, Open, Two-Cohort Phase 2 Study. BMC Med., 23.","DOI":"10.1186\/s12916-025-04404-4"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41392-023-01317-7","article-title":"Toripalimab Combined with Lenvatinib and GEMOX Is a Promising Regimen as First-Line Treatment for Advanced Intrahepatic Cholangiocarcinoma: A Single-Center, Single-Arm, Phase 2 Study","volume":"8","author":"Shi","year":"2023","journal-title":"Sig Transduct. Target. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S2468-1253(22)00043-7","article-title":"Gemcitabine and Cisplatin plus Durvalumab with or without Tremelimumab in Chemotherapy-Naive Patients with Advanced Biliary Tract Cancer: An Open-Label, Single-Centre, Phase 2 Study","volume":"7","author":"Oh","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Macarulla, T., Ren, Z., Chon, H.J., Park, J.O., Kim, J.W., Pressiani, T., Li, D., Zhukova, L., Zhu, A.X., and Chen, M.-H. (2024). Atezolizumab Plus Chemotherapy with or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial. J. Clin. Oncol.","DOI":"10.1200\/JCO.24.00337"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"TPS4187","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS4187","article-title":"GEMINI-Hepatobiliary: A Phase 2 Study of Novel First-Line Immuno-Oncology-Based Treatments in Patients with Advanced Hepatobiliary Cancers","volume":"42","author":"Zhou","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4080","DOI":"10.1200\/JCO.2025.43.16_suppl.4080","article-title":"First-Line Rilvegostomig (Rilve) plus Chemotherapy (CTx) in Advanced Biliary Tract Cancer (BTC): Primary Analysis of GEMINI-Hepatobiliary Substudy 2 Cohort A","volume":"43","author":"Zhou","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_111","unstructured":"(2026, April 15). AstraZeneca Phase III, Randomized, Open-Label, Global, Multicenter Study of Rilvegostomig or Durvalumab in Combination with Chemotherapy as a First-Line Treatment for Patients with Advanced Biliary Tract Cancer (ARTEMIDE-Biliary02), Available online: https:\/\/clinicaltrials.gov\/study\/NCT07221253."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Wang, Z., Li, L., Huang, P., Tu, H., Zhang, X., Yu, L., Liang, F., Huang, C., Qiu, S., and Ye, Q. (2025). Adjuvant Camrelizumab Combined with Capecitabine in Patients with Intrahepatic Cholangiocarcinoma after Surgical Resection in China (ACC): A Single-Arm, Single-Centre, Open-Label, Phase 2 Trial. Lancet Gastroenterol. Hepatol., 124\u2013136.","DOI":"10.1016\/S2468-1253(25)00268-7"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1001\/jamaoncol.2025.1926","article-title":"Adjuvant Chemoradiation and Immunotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Cancer: A Randomized Clinical Trial","volume":"11","author":"Xiao","year":"2025","journal-title":"JAMA Oncol."},{"key":"ref_114","unstructured":"(2026, January 09). The First Affiliated Hospital with Nanjing Medical University A Phase 2, Randomized, Controlled, Multicenter Study of Adjuvant Adebrelimab Combined with Capecitabine in Resected Cholangiocarcinoma with High-Risk Factors: ACHIEVE, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06607276."},{"key":"ref_115","unstructured":"(2026, January 09). Institut f\u00fcr Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest A Phase II Study of Immunotherapy with Durvalumab and Tremelimumab in Combination with Capecitabine or Without Capecitabine in Adjuvant Situation for Biliary Tract Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05239169."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2021619","DOI":"10.1080\/2162402X.2021.2021619","article-title":"Immunomodulation via FGFR Inhibition Augments FGFR1 Targeting T-Cell Based Antitumor Immunotherapy for Head and Neck Squamous Cell Carcinoma","volume":"11","author":"Kono","year":"2022","journal-title":"Oncoimmunology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1158\/2326-6066.CIR-18-0595","article-title":"The Combined Effect of FGFR Inhibition and PD-1 Blockade Promotes Tumor-Intrinsic Induction of Antitumor Immunity","volume":"7","author":"Palakurthi","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"103625","DOI":"10.1016\/j.esmoop.2024.103625","article-title":"Open-Label, Dose-Escalation FIGHT-101 Study of Pemigatinib Combined with Targeted Therapy, Chemotherapy, or Immunotherapy in Patients with Advanced Malignancies","volume":"9","author":"Saleh","year":"2024","journal-title":"ESMO Open"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Wang, G., Du, L., Zhao, J., Pan, L., Zhang, G., Wang, F., and Liu, R. (2023). Case Report: Persistent Response to Combination Therapy of Pemigatinib, Chemotherapy, and Immune Checkpoint Inhibitor in a Patient with Advanced Intrahepatic Cholangiocarcinoma. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1124482"},{"key":"ref_120","unstructured":"(2026, April 18). Pemigatinib and Atezolizumab with or Without Bevacizumab for Treatment of Patients with Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion\u2014NCI, Available online: https:\/\/www.cancer.gov\/research\/participate\/clinical-trials-search\/v?id=NCI-2024-04693."},{"key":"ref_121","unstructured":"(2026, April 18). Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Prospective, Single-Arm, Multicenter Phase II Study of Evaluation of the Efficacy and Safety of Pemigatinib Combined with PD-1 Inhibitor in First-Line Treatment of Unresectable or Metastatic Intrahepatic Cholangiocarcinoma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05913661."},{"key":"ref_122","unstructured":"Feng, S. (2026, April 18). Pemigatinib Combined with Durvalumab for the Safety and Efficacy in Second-Line Treatment of Biliary Tract Cancer: A Single-Arm, Multicenter Phase II Clinical Trial, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06530823."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"oyaf362","DOI":"10.1093\/oncolo\/oyaf362","article-title":"Clinical and Translational Study of Ivosidenib plus Nivolumab in Advanced Solid Tumors Harboring IDH1 Mutations","volume":"30","author":"Nguyen","year":"2025","journal-title":"Oncologist"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"TPS4197","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS4197","article-title":"A Phase 1\/2, Safety Lead-in and Dose Expansion, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination with Nivolumab and Ipilimumab in Previously Treated Subjects with IDH1-Mutated Nonresectable or Metastatic Cholangiocarcinoma","volume":"42","author":"Kelley","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1093\/jnci\/djad118","article-title":"Radiation Dose, Schedule, and Novel Systemic Targets for Radio-Immunotherapy Combinations","volume":"115","author":"Karapetyan","year":"2023","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI67313","article-title":"Irradiation and Anti\u2013PD-L1 Treatment Synergistically Promote Antitumor Immunity in Mice","volume":"124","author":"Deng","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e352","DOI":"10.1016\/S1470-2045(24)00075-5","article-title":"Radiotherapy, Immunity, and Immune Checkpoint Inhibitors","volume":"25","author":"Lynch","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1001\/jamaoncol.2019.3702","article-title":"Radioembolization Plus Chemotherapy for First-Line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial","volume":"6","author":"Edeline","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_129","unstructured":"Bullock, A. (2026, February 27). A Single Arm Phase 2 Study of Y-90 SIRT in Combination with Durvalumab (MEDI 4736) and Gemcitabine\/Cisplatin in Locally Advanced, Unresectable or Metastatic Intrahepatic Cholangiocarcinoma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05655949."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.annonc.2022.05.519","article-title":"Pembrolizumab in Microsatellite Instability High or Mismatch Repair Deficient Cancers: Updated Analysis from the Phase II KEYNOTE-158 Study","volume":"33","author":"Maio","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_131","first-page":"e2400475","article-title":"PD-L1 Expression in Biliary Tract Cancer: Comparison Across Antibody Clones and Role as a Predictor of Response to Chemoimmunotherapy: A Meta-Analysis","volume":"9","author":"Osataphan","year":"2025","journal-title":"JCO Precis. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Liddell, S.S., Chakrabarti, S., Wintheiser, G.A., Zemla, T.J., Shi, Q., Tella, S.H., Jin, Z., Wookey, V.B., Hassan, H., and Tran, N.H. (2022). Tumor Mutational Burden Is a Potential Predictive Biomarker for Response to Immune Checkpoint Inhibitors in Patients with Advanced Biliary Tract Cancer. JCO Precis. Oncol., e2200003.","DOI":"10.1200\/PO.22.00003"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1056\/NEJMc1713444","article-title":"Tumor Mutational Burden and Response Rate to PD-1 Inhibition","volume":"377","author":"Yarchoan","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1172\/JCI91190","article-title":"IFN-\u03b3-Related mRNA Profile Predicts Clinical Response to PD-1 Blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Shang, T., Jiang, T., Lu, T., Wang, H., Cui, X., Pan, Y., Xu, M., Pei, M., Ding, Z., and Feng, X. (2023). Tertiary Lymphoid Structures Predict the Prognosis and Immunotherapy Response of Cholangiocarcinoma. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1166497"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3350\/cmh.2024.0895","article-title":"Radiogenomics of Intrahepatic Cholangiocarcinoma Predicts Immunochemotherapy Response and Identifies Therapeutic Target","volume":"31","author":"Ji","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Xu, J., Ji, Y., Feng, M., Zhang, Z., and Yu, D. (2026). Gemcitabine-Cisplatin plus Durvalumab in Advanced Intrahepatic Cholangiocarcinoma: Effectiveness Outcomes and Characterization of the Tumor Microenvironment. Hepatol. Int.","DOI":"10.1007\/s12072-026-11070-y"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00262-024-03878-0","article-title":"The Correlation between LAG-3 Expression and the Efficacy of Chemoimmunotherapy in Advanced Biliary Tract Cancer","volume":"74","author":"Tang","year":"2025","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1136\/gutjnl-2025-334861","article-title":"Immunosuppressive Contribution of Tumour-Infiltrating B Cells in Human Intrahepatic Cholangiocarcinoma and Their Role in Chemoimmunotherapy Outcome","volume":"75","author":"Milardi","year":"2025","journal-title":"Gut"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"101557","DOI":"10.1016\/j.jhepr.2025.101557","article-title":"A Pathomics-Integrated Multimodal Model to Evaluate Chemoimmunotherapy Efficacy in Unresectable Intrahepatic Cholangiocarcinoma","volume":"7","author":"Cao","year":"2025","journal-title":"JHEP Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"116035","DOI":"10.1016\/j.ejca.2025.116035","article-title":"Genomic Pathway Alterations and Their Prognostic Impact in Biliary Tract Cancer: Insights from a Multinational Cohort Treated with Cisplatin, Gemcitabine, and Durvalumab","volume":"230","author":"Pirrone","year":"2025","journal-title":"Eur. J. Cancer"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00535-025-02320-1","article-title":"TP53 Mutation Predicts Resistance to Immune Checkpoint Inhibitor-Based Therapy in Intrahepatic Cholangiocarcinoma","volume":"61","author":"Inada","year":"2026","journal-title":"J. Gastroenterol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.annonc.2022.09.150","article-title":"The Clinical Landscape of Cell-Free DNA Alterations in 1671 Patients with Advanced Biliary Tract Cancer","volume":"33","author":"Berchuck","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jhep.2024.10.043","article-title":"Circulating Tumor DNA Status and Dynamics Predict Recurrence in Patients with Resected Extrahepatic Cholangiocarcinoma","volume":"82","author":"Yoo","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Boute, M., Senechal, V., Gerstenberg, A., and Ramos, C. (2024). Intracellular Cytokine Profiling and Specific Immune Cell Characterization Using CyTOF in Whole Blood for Antibody-Based Cancer Immunotherapies. J. Immunother. Cancer, 12.","DOI":"10.1136\/jitc-2024-SITC2024.0056"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"An, H.J., Chon, H.J., and Kim, C. (2021). Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179414"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"33789","DOI":"10.1038\/srep33789","article-title":"Prognostic Significance of Neutrophil to Lymphocyte Ratio in Oncologic Outcomes of Cholangiocarcinoma: A Meta-Analysis","volume":"6","author":"Tan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"12691","DOI":"10.1038\/s41598-022-16727-w","article-title":"The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Cholangiocarcinoma: A Systematic Review and Meta-Analysis","volume":"12","author":"Liu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"111384","DOI":"10.1016\/j.celrep.2022.111384","article-title":"Circulating Monocytes Associated with Anti-PD-1 Resistance in Human Biliary Cancer Induce T Cell Paralysis","volume":"40","author":"Keenan","year":"2022","journal-title":"Cell Rep."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Fan, R., Lv, Z., Wang, T., Chen, W., Han, W., and Mei, Q. (2026). A Compass in the Challenge: The CALLY Index as a Prognostic Biomarker in Advanced Cholangiocarcinoma Treated with Chemoimmunotherapy: A Retrospective Propensity Score-Matched Cohort Study. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1713495"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Damei, I., Trickovic, T., Mami-Chouaib, F., and Corgnac, S. (2023). Tumor-Resident Memory T Cells as a Biomarker of the Response to Cancer Immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1205984"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"10807","DOI":"10.1038\/s41598-023-37736-3","article-title":"Peripheral CD4 Memory T Cells Predict the Efficacy of Immune Checkpoint Inhibitor Therapy in Patients with Non-Small Cell Lung Cancer","volume":"13","author":"Inomata","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Rizzo, A., Ricci, A.D., and Brandi, G. (2021). PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer. Cancers, 13.","DOI":"10.3390\/cancers13030558"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1097\/HEP.0000000000000688","article-title":"Immunogenomics of Cholangiocarcinoma","volume":"82","author":"Gehl","year":"2025","journal-title":"Hepatology"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Yu, X., Zhu, L., Wang, T., and Chen, J. (2023). Immune Microenvironment of Cholangiocarcinoma: Biological Concepts and Treatment Strategies. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1037945"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Nishida, N., Aoki, T., Morita, M., Chishina, H., Takita, M., Ida, H., Hagiwara, S., Minami, Y., Ueshima, K., and Kudo, M. (2023). Non-Inflamed Tumor Microenvironment and Methylation\/Downregulation of Antigen-Presenting Machineries in Cholangiocarcinoma. Cancers, 15.","DOI":"10.3390\/cancers15082379"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e004892","DOI":"10.1136\/jitc-2022-004892","article-title":"Multimodule Characterization of Immune Subgroups in Intrahepatic Cholangiocarcinoma Reveals Distinct Therapeutic Vulnerabilities","volume":"10","author":"Lin","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1158\/1078-0432.CCR-21-1804","article-title":"Cancer Immunoediting in the Era of Immuno-Oncology","volume":"8","author":"Gubin","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1604958","article-title":"Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma","volume":"375","author":"Zaretsky","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12943-024-02212-7","article-title":"Resistance Mechanisms to Immune Checkpoint Inhibitors: Updated Insights","volume":"24","author":"Alsaafeen","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1158\/2159-8290.CD-17-0593","article-title":"Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer","volume":"7","author":"Gettinger","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"10501","DOI":"10.1038\/ncomms10501","article-title":"Adaptive Resistance to Therapeutic PD-1 Blockade Is Associated with Upregulation of Alternative Immune Checkpoints","volume":"7","author":"Koyama","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4","DOI":"10.32604\/or.2025.070505","article-title":"The Frontier of Melanoma Treatment: Defeating Immunotherapy Resistance-A Systematic Review","volume":"34","author":"Mozga","year":"2026","journal-title":"Oncol. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s43556-025-00267-6","article-title":"TIM-3 Teams up with PD-1 in Cancer Immunotherapy: Mechanisms and Perspectives","volume":"6","author":"Yan","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"101184","DOI":"10.1016\/j.esmoop.2023.101184","article-title":"Anti-TIGIT Therapies for Solid Tumors: A Systematic Review","volume":"8","author":"Rousseau","year":"2023","journal-title":"ESMO Open"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41571-021-00552-7","article-title":"Enhancing Immunotherapy in Cancer by Targeting Emerging Immunomodulatory Pathways","volume":"19","author":"Kraehenbuehl","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1158\/1078-0432.CCR-24-1660","article-title":"Facts and Hopes of CD40 Agonists in Cancer Immunotherapy","volume":"31","author":"McVey","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(24)02722-3","article-title":"Ivonescimab versus Pembrolizumab for PD-L1-Positive Non-Small Cell Lung Cancer (HARMONi-2): A Randomised, Double-Blind, Phase 3 Study in China","volume":"405","author":"Xiong","year":"2025","journal-title":"Lancet"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/s41551-025-01569-4","article-title":"A Trispecific Antibody Engaging T Cells with Tumour and Myeloid Cells Augments Antitumour Immunity","volume":"10","author":"Yang","year":"2025","journal-title":"Nat. Biomed. Eng."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/nature25501","article-title":"TGF\u03b2 Attenuates Tumour Response to PD-L1 Blockade by Contributing to Exclusion of T Cells","volume":"554","author":"Mariathasan","year":"2018","journal-title":"Nature"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nature25492","article-title":"TGF\u03b2 Drives Immune Evasion in Genetically Reconstituted Colon Cancer Metastasis","volume":"554","author":"Tauriello","year":"2018","journal-title":"Nature"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1007\/s00262-023-03430-6","article-title":"First-in-Human Study of Oleclumab, a Potent, Selective Anti-CD73 Monoclonal Antibody, Alone or in Combination with Durvalumab in Patients with Advanced Solid Tumors","volume":"72","author":"Bendell","year":"2023","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1080\/14796694.2024.2354160","article-title":"PACIFIC-9: Phase III Trial of Durvalumab + Oleclumab or Monalizumab in Unresectable Stage III Non-Small-Cell Lung Cancer","volume":"20","author":"Barlesi","year":"2024","journal-title":"Future Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"e2518440","DOI":"10.1001\/jamanetworkopen.2025.18440","article-title":"Durvalumab Alone or Combined with Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer: Update From the COAST Randomized Clinical Trial","volume":"8","author":"Aggarwal","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1158\/0008-5472.CAN-21-4141","article-title":"Cancer-Associated Fibroblasts Suppress CD8+ T-Cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade","volume":"82","author":"Jenkins","year":"2022","journal-title":"Cancer Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1016\/j.cell.2021.07.020","article-title":"Targeting Pin1 Renders Pancreatic Cancer Eradicable by Synergizing with Immunochemotherapy","volume":"184","author":"Koikawa","year":"2021","journal-title":"Cell"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1158\/0008-5472.CAN-24-0940","article-title":"Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer","volume":"84","author":"Cui","year":"2024","journal-title":"Cancer Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1158\/0008-5472.CAN-19-3158","article-title":"NOX4 Inhibition Potentiates Immunotherapy by Overcoming Cancer-Associated Fibroblast-Mediated CD8 T-Cell Exclusion from Tumors","volume":"80","author":"Ford","year":"2020","journal-title":"Cancer Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1126\/science.1251102","article-title":"Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer","volume":"344","author":"Tran","year":"2014","journal-title":"Science"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"e005755","DOI":"10.1136\/jitc-2022-005755","article-title":"Efficacy and Safety of Lifileucel, a One-Time Autologous Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy, in Patients with Advanced Melanoma after Progression on Immune Checkpoint Inhibitors and Targeted Therapies: Pooled Analysis of Consecutive Cohorts of the C-144-01 Study","volume":"10","author":"Chesney","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Woodford, R., Lorigan, P., Oudit, D., Abdulgawad, A., Thistlethwaite, F., and Lim, K.H.J. (2026). Tumour-Infiltrating Lymphocyte Therapy in Melanoma: Ready for Prime Time?. Br. J. Cancer, 1501\u20131509.","DOI":"10.1038\/s41416-026-03350-z"},{"key":"ref_183","unstructured":"Kammula, U. (2026, February 27). A Phase 2 Study to Evaluate the Efficacy and Safety of Adoptive Transfer of Autologous Tumor Infiltrating Lymphocytes in Patients with Locally Advanced, Recurrent, or Metastatic Biliary Tract Cancers, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03801083."},{"key":"ref_184","unstructured":"Intima Bioscience, Inc. (2026, April 22). A Phase I\/II Trial in Patients with Metastatic Gastrointestinal Epithelial Cancer Administering Tumor-Infiltrating Lymphocytes in Which the Gene Encoding CISH Was Inactivated Using the CRISPR\/Cas9 System, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04426669."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13045-016-0378-7","article-title":"Cocktail Treatment with EGFR-Specific and CD133-Specific Chimeric Antigen Receptor-Modified T Cells in a Patient with Advanced Cholangiocarcinoma","volume":"10","author":"Feng","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1158\/1078-0432.CCR-17-0432","article-title":"Phase I Study of Chimeric Antigen Receptor\u2013Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers","volume":"24","author":"Guo","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1007\/s13238-017-0440-4","article-title":"Phase I Study of Chimeric Antigen Receptor Modified T Cells in Treating HER2-Positive Advanced Biliary Tract Cancers and Pancreatic Cancers","volume":"9","author":"Feng","year":"2018","journal-title":"Protein Cell"},{"key":"ref_188","unstructured":"UTC Therapeutics Inc. (2026, February 27). A First-In-Human, Single Arm, Open-Label, Phase 1 Dose-Escalation Study of UCMYM802 Injection in Mesothelin-Positive Advanced Malignant Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06256055."},{"key":"ref_189","unstructured":"(2026, April 22). Verismo Therapeutics A Phase 1 Study of SynKIR-110, Autologous T Cells Transduced with Mesothelin KIR-CAR, in Subjects with Mesothelin-Expressing Advanced Ovarian Cancer, Cholangiocarcinoma, or Mesothelioma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05568680."},{"key":"ref_190","unstructured":"Chongqing Precision Biotech Co., Ltd. (2026, April 22). Phase I Clinical Study of Chimeric Antigen Receptor T Cells (C-13-60) in the Treatment of Carcinoembryonic Antigen (CEA) Positive Advanced Malignant Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06043466."},{"key":"ref_191","unstructured":"Fang, W. (2026, April 22). Exploratory Study on the Safety and Preliminary Efficacy of UCLH80-1 Cells in Patients with CDH17-Positive Advanced Malignant Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06937567."},{"key":"ref_192","unstructured":"(2026, April 22). Second Affiliated Hospital, School of Medicine, Zhejiang University Safety and Efficacy Evaluation of MUC-1 CART in the Treatment of Intrahepatic Cholangiocarcinoma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03633773."},{"key":"ref_193","unstructured":"(2026, April 22). Carisma Therapeutics Inc A Phase 1, First in Human Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor in Subjects with HER2 Overexpressing Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04660929."},{"key":"ref_194","unstructured":"Newish Technology (Beijing) Co., Ltd. (2026, April 22). Clinical Trial of Autologous Tcm Cellular Immunotherapy Combined with Traditional Therapy in Intrahepatic Cholangiocarcinoma Patients After Radical Resection, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03820310."},{"key":"ref_195","unstructured":"Wongkajornsilp, A. (2026, April 22). Phase 1 Study of The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous Cytokine-Induced Killer Cells, Available online: https:\/\/clinicaltrials.gov\/study\/NCT01868490."},{"key":"ref_196","first-page":"429","article-title":"Neoantigen Identification and TCR-T Therapy Development for Solid Tumors: Current Advances and Future Perspectives","volume":"5","author":"Zheng","year":"2025","journal-title":"J. Natl. Cancer Cent."},{"key":"ref_197","unstructured":"(2026, February 27). Providence Health & Services A Phase I\/Ib Study of Adoptively Transferred T-Cell Receptor Gene-Engineered T Cells (TCR-T) Targeting Patient-Unique Tumor-Specific Neoantigens, with in Vivo CD40 Activation and PD-1 Blockade, for Patients with Incurable Cancers, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05349890."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1038\/s41591-023-02452-y","article-title":"Mesothelin-Targeting T Cell Receptor Fusion Construct Cell Therapy in Refractory Solid Tumors: Phase 1\/2 Trial Interim Results","volume":"29","author":"Hassan","year":"2023","journal-title":"Nat. Med."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Leem, G., Jang, S.-I., Cho, J.-H., Jo, J.H., Lee, H.S., Chung, M.J., Park, J.Y., Bang, S., Yoo, D.-K., and Cheon, H.-C. (2022). Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1\/2a Trial. Cancers, 14.","DOI":"10.3390\/cancers14174229"},{"key":"ref_200","unstructured":"(2026, April 18). Institut f\u00fcr Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest A Phase II Single-Arm, Open-Label Study of Atezolizumab and Derazantinib for Patients with Advanced Intrahepatic Cholangiocarcinoma with FGFR2, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05174650."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.jhep.2020.11.037","article-title":"CD40-Mediated Immune Cell Activation Enhances Response to Anti-PD-1 in Murine Intrahepatic Cholangiocarcinoma","volume":"74","author":"Diggs","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_202","unstructured":"(2026, June 10). A Study of CDX-1140, a CD40 Agonist, in Combination with Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects with Biliary Tract Carcinoma (BTC)\u2014NCI, Available online: https:\/\/www.cancer.gov\/research\/participate\/clinical-trials-search\/v?id=NCI-2023-03936."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s11523-025-01130-y","article-title":"A Phase 1b\/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors","volume":"20","author":"Eng","year":"2025","journal-title":"Target. Oncol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/S1470-2045(21)00584-2","article-title":"Evorpacept Alone and in Combination with Pembrolizumab or Trastuzumab in Patients with Advanced Solid Tumours (ASPEN-01): A First-in-Human, Open-Label, Multicentre, Phase 1 Dose-Escalation and Dose-Expansion Study","volume":"22","author":"Lakhani","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"TPS631","DOI":"10.1200\/JCO.2023.41.4_suppl.TPS631","article-title":"A Phase I\/II Study of the CXCR2 Inhibitor, AZD5069, in Combination with Durvalumab, in Patients (Pts) with Advanced Hepatocellular Carcinoma (HCC)","volume":"41","author":"Evans","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_206","first-page":"955","article-title":"A Phase I\/II Study of a MUC1 Peptide Pulsed Autologous Dendritic Cell Vaccine as Adjuvant Therapy in Patients with Resected Pancreatic and Biliary Tumors","volume":"6","author":"Lepisto","year":"2008","journal-title":"Cancer Ther."},{"key":"ref_207","first-page":"3575","article-title":"MUC1 Peptide Vaccination in Patients with Advanced Pancreas or Biliary Tract Cancer","volume":"25","author":"Yamamoto","year":"2005","journal-title":"Anticancer. Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1007\/s11605-013-2286-2","article-title":"Dendritic Cell-Based Immunotherapy Targeting Synthesized Peptides for Advanced Biliary Tract Cancer","volume":"17","author":"Kobayashi","year":"2013","journal-title":"J. Gastrointest. Surg."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00534-011-0437-y","article-title":"Clinical Utilization of Postoperative Dendritic Cell Vaccine plus Activated T-Cell Transfer in Patients with Intrahepatic Cholangiocarcinoma","volume":"19","author":"Shimizu","year":"2012","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1158\/1078-0432.CCR-12-3592","article-title":"Long-Term Vaccination with Multiple Peptides Derived from Cancer-Testis Antigens Can Maintain a Specific T-Cell Response and Achieve Disease Stability in Advanced Biliary Tract Cancer","volume":"19","author":"Aruga","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"e012107","DOI":"10.1136\/jitc-2025-012107","article-title":"Exceptional Tumor-Free Survival of a Patient with Metastatic Intrahepatic Cholangiocarcinoma after Surgery and Personalized Peptide Vaccination: Revisiting a Striking Case","volume":"13","author":"Maia","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.jhep.2016.06.027","article-title":"Personalized Peptide Vaccine-Induced Immune Response Associated with Long-Term Survival of a Metastatic Cholangiocarcinoma Patient","volume":"65","author":"Chandran","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/s41591-023-02760-3","article-title":"Lymph-Node-Targeted, mKRAS-Specific Amphiphile Vaccine in Pancreatic and Colorectal Cancer: The Phase 1 AMPLIFY-201 Trial","volume":"30","author":"Pant","year":"2024","journal-title":"Nat. Med."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1038\/s41591-025-03876-4","article-title":"Lymph Node-Targeted, mKRAS-Specific Amphiphile Vaccine in Pancreatic and Colorectal Cancer: Phase 1 AMPLIFY-201 Trial Final Results","volume":"31","author":"Wainberg","year":"2025","journal-title":"Nat. Med."},{"key":"ref_215","unstructured":"(2026, April 22). Elicio Therapeutics First in Human Phase 1\/2 Trial of ELI-002 7P Immunotherapy as Treatment for Subjects with Kirsten Rat Sarcoma (KRAS)\/Neuroblastoma RAS Viral Oncogene Homolog (NRAS) Mutated Pancreatic Ductal Adenocarcinoma (PDAC) and Other Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05726864."},{"key":"ref_216","unstructured":"(2026, April 22). Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins A Pilot Study of Targeting Driver Oncogenes with a Peptide Vaccine Plus Durvalumab and Tremelimumab for Patients with Biliary Tract Cancers, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06564623."},{"key":"ref_217","unstructured":"Chun-Nan, Y. (2026, April 22). A Single-Arm, Phase 2 Study to Evaluate OBI-833\/OBI-821 Maintenance Therapy in Patients with Globo H-Positive Advanced Biliary Tract Cancer Not Progresseding Under First-Line Gemcitabine and Cisplatin, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06490198."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12943-021-01342-6","article-title":"Identification of Tumor Antigens and Immune Subtypes of Cholangiocarcinoma for mRNA Vaccine Development","volume":"20","author":"Huang","year":"2021","journal-title":"Mol. Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/12\/2001\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:36:14Z","timestamp":1782196574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/12\/2001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,20]]},"references-count":218,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cancers18122001"],"URL":"https:\/\/doi.org\/10.3390\/cancers18122001","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,20]]}}}