{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:10:34Z","timestamp":1783933834475,"version":"3.55.0"},"reference-count":136,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal and heterogeneous primary liver malignancy with a dismal prognosis. Approximately 70% of patients are diagnosed at locally advanced or metastatic stages, therefore missing the opportunity for curative surgery, and conventional chemotherapy offers limited survival benefits. Immunotherapy, especially immune checkpoint blockade, represents a promising strategy, yet its efficacy as monotherapy in iCCA remains modest primarily due to the profoundly immunosuppressive and desmoplastic tumor microenvironment. This review examines the immune cell infiltration landscape of iCCA, focusing on the distinct roles of lymphoid cells and myeloid cells in shaping immune evasion. We then analyze key factors affecting immune responses, such as tumor-intrinsic driver mutations, immune regulatory mechanisms, and acquired resistance. Furthermore, we summarize current clinical advances in iCCA immunotherapy, including immune checkpoint inhibitor monotherapy, bispecific antibodies, combination strategies with chemotherapy or targeted therapy, cancer vaccines, and adoptive cell therapy. Despite some progress, the overall response to immunotherapy remains suboptimal, and future strategies need to focus on deciphering context-specific resistance mechanisms and enhancing the tumor-specific immune response.<\/jats:p>","DOI":"10.3390\/ijms27146228","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:53:58Z","timestamp":1783932838000},"page":"6228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Immunotherapy for Intrahepatic Cholangiocarcinoma"],"prefix":"10.3390","volume":"27","author":[{"given":"Huimin","family":"Qi","sequence":"first","affiliation":[{"name":"Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Pan","sequence":"additional","affiliation":[{"name":"Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3517-4230","authenticated-orcid":false,"given":"Hailong","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"},{"name":"Shanghai Key Laboratory of Molecular Imaging and Digital and Intelligent Empowerment Biomedical Innovation Center, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1097\/PAS.0000000000001118","article-title":"Intrahepatic Cholangiocarcinomas Have Histologically and Immunophenotypically Distinct Small and Large Duct Patterns","volume":"42","author":"Sigel","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.molmed.2025.01.008","article-title":"Molecular subtypes of intrahepatic cholangiocarcinoma","volume":"31","author":"Zhu","year":"2025","journal-title":"Trends Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/his.13975","article-title":"The 2019 WHO classification of tumours of the digestive system","volume":"76","author":"Nagtegaal","year":"2020","journal-title":"Histopathology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.hpb.2019.10.009","article-title":"Clinicopathological characteristics of intrahepatic cholangiocarcinoma according to gross morphologic type: Cholangiolocellular differentiation traits and inflammation- and proliferation-phenotypes","volume":"22","author":"Chung","year":"2020","journal-title":"HPB"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hou, W. (2025). Role of TGF\u03b2-activated cancer-associated fibroblasts in the resistance to checkpoint blockade immunotherapy. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1602452"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/liv.14098","article-title":"The tumour microenvironment and immune milieu of cholangiocarcinoma","volume":"39","author":"Fabris","year":"2019","journal-title":"Liver Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.jhep.2022.11.030","article-title":"Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma","volume":"78","author":"Kendre","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1200\/JCO.2023.41.4_suppl.607","article-title":"Clinical and mutational profiles of microsatellite instability (MSI-H) in intrahepatic cholangiocarcinoma (iCCA)","volume":"41","author":"Eluri","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e35726","DOI":"10.1002\/cncr.35726","article-title":"DNA damage response and repair gene mutations predict clinical outcomes in biliary tract cancer","volume":"131","author":"Tan","year":"2025","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1097\/JS9.0000000000001022","article-title":"Worldwide research trends on tumor burden and immunotherapy: A bibliometric analysis","volume":"110","author":"Zhang","year":"2024","journal-title":"Int. J. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jhep.2019.03.013","article-title":"Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma","volume":"71","author":"Bertuccio","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/liv.14089","article-title":"Surgery for cholangiocarcinoma","volume":"39","author":"Cillo","year":"2019","journal-title":"Liver Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1245\/s10434-024-14972-z","article-title":"ASO Author Reflections: Minimally Invasive Approach and Oncologic Benefit in Intrahepatic Cholangiocarcinoma (iCCA) With Risk of Very Early Recurrence: Is it Time to Consider Technique as a Key Element of Onco-Surgical Strategy?","volume":"31","author":"Ratti","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1666393","DOI":"10.3389\/fimmu.2025.1666393","article-title":"Gemcitabine-cisplatin chemotherapy plus anti-PD-L1 therapy reinvigorates antitumor immune response by reprogramming the intrahepatic cholangiocarcinoma microenvironment","volume":"16","author":"Song","year":"2025","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.trecan.2019.05.010","article-title":"Integrative Approaches to Cancer Immunotherapy","volume":"5","author":"Szeto","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_16","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":"2019","journal-title":"Hepatology"},{"key":"ref_17","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_18","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":"2021","journal-title":"Hepatology"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"100401","DOI":"10.1016\/j.modpat.2023.100401","article-title":"Correlation of Vein-Rich Tumor Microenvironment of Intrahepatic Cholangiocarcinoma With Tertiary Lymphoid Structures and Patient Outcome","volume":"37","author":"Doi","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.dld.2025.04.013","article-title":"The intratumoral balance of IgG4+ plasma cells and CD8+ T cells is associated with prognosis of intrahepatic cholangiocarcinoma after curative resection","volume":"57","author":"Ye","year":"2025","journal-title":"Dig. Liver Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.3748\/wjg.v26.i33.4900","article-title":"Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells","volume":"26","author":"Polidoro","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2035919","DOI":"10.1080\/2162402X.2022.2035919","article-title":"MICA\/B-targeted antibody promotes NK cell\u2013driven tumor immunity in patients with intrahepatic cholangiocarcinoma","volume":"11","author":"Oliviero","year":"2022","journal-title":"OncoImmunology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/cas.14267","article-title":"Endogenous CXCL9 affects prognosis by regulating tumor-infiltrating natural killer cells in intrahepatic cholangiocarcinoma","volume":"111","author":"Fukuda","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Meng, X.-L., Lu, J.-C., Zhang, Y.-X., Pu, P., Guo, X.-J., Zhu, T., Hu, Z.-Q., Yu, L., Sun, Q.-M., and Gao, Q. (2026). Norepinephrine promotes tumour cell aggressiveness and NK cell ferroptosis via ADRB2 in intrahepatic cholangiocarcinoma with perineural invasion. Gut.","DOI":"10.1136\/gutjnl-2025-337595"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101954","DOI":"10.1016\/j.tranon.2024.101954","article-title":"Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF","volume":"44","author":"Zhang","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13045-024-01559-0","article-title":"Deciphering the performance of macrophages in tumour microenvironment: A call for precision immunotherapy","volume":"17","author":"Toledo","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00432-024-05888-y","article-title":"Small duct and large duct type intrahepatic cholangiocarcinoma reveal distinct patterns of immune signatures","volume":"150","author":"Bernatz","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_29","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":"2020","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00148","DOI":"10.1002\/advs.202500148","article-title":"Role of Tunneling Nanotubes in Arachidonic Acid Transfer and Macrophage Function Reprogramming in Intrahepatic Cholangiocarcinoma","volume":"12","author":"Chen","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s40364-024-00648-z","article-title":"Spatial resolved transcriptomics reveals distinct cross-talk between cancer cells and tumor-associated macrophages in intrahepatic cholangiocarcinoma","volume":"12","author":"Dong","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41392-026-02657-w","article-title":"MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumor growth","volume":"11","author":"Zhuravleva","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/liv.15383","article-title":"DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti-DKK1 therapeutic DKN-01","volume":"43","author":"Jarman","year":"2022","journal-title":"Liver Int."},{"key":"ref_34","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_35","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_36","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41420-024-02079-z","article-title":"Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma","volume":"10","author":"Sun","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e70076","DOI":"10.1111\/imr.70076","article-title":"Thymic Dendritic Cells Revisited","volume":"336","author":"Xuan","year":"2025","journal-title":"Immunol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pei, D.-N., Song, Y., Zhou, Y.-X., Shu, B., Huang, S.-W., Li, F.-Z., Dai, W.-D., and Sun, B.-Y. (2025). Enhancing cDC1-mediated anti-tumor immunity limits tumor progression and potentiates anti-PD-1 therapy in intrahepatic cholangiocarcinoma. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1708962"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41392-021-00670-9","article-title":"Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.4049\/jimmunol.1500959","article-title":"Expression of Cationic Amino Acid Transporter 2 Is Required for Myeloid-Derived Suppressor Cell\u2013Mediated Control of T Cell Immunity","volume":"195","author":"Bozkus","year":"2015","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 is a novel direct target of HIF-1\u03b1, and its blockade under hypoxia enhanced MDSC-mediated T cell activation","volume":"211","author":"Noman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10113","DOI":"10.1073\/pnas.0711106105","article-title":"Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation","volume":"105","author":"Onishi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ricci, A.D., Rizzo, A., Schirizzi, A., D\u2019alessandro, R., Frega, G., Brandi, G., Shahini, E., Cozzolongo, R., Lotesoriere, C., and Giannelli, G. (2024). Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Regulatory Mechanisms, Functions, and Therapeutic Implications. Cancers, 16.","DOI":"10.3390\/cancers16203542"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1002\/eji.201141532","article-title":"Human tumor-induced and naturally occurring Treg cells differentially affect NK cells activated by either IL-2 or target cells","volume":"41","author":"Bergmann","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1084\/jem.20051511","article-title":"CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner","volume":"202","author":"Ghiringhelli","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41577-019-0210-z","article-title":"Dendritic cells in cancer immunology and immunotherapy","volume":"20","author":"Wculek","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","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_48","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_49","doi-asserted-by":"crossref","unstructured":"Cammarota, A., Balsano, R., Pressiani, T., Bozzarelli, S., Rimassa, L., and Lleo, A. (2025). The Immune\u2013Genomics of Cholangiocarcinoma: A Biological Footprint to Develop Novel Immunotherapies. Cancers, 17.","DOI":"10.3390\/cancers17020272"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1158\/1078-0432.CCR-14-3296","article-title":"Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma","volume":"22","author":"Moeini","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_51","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_52","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_53","doi-asserted-by":"crossref","first-page":"e1734","DOI":"10.1093\/oncolo\/oyae170","article-title":"FGFR2 fusion\/rearrangement is associated with favorable prognosis and immunoactivation in patients with intrahepatic cholangiocarcinoma","volume":"29","author":"Liu","year":"2024","journal-title":"Oncologist"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1758835920953293","DOI":"10.1177\/1758835920953293","article-title":"FGFR inhibitors in cholangiocarcinoma: What\u2019s now and what\u2019s next?","volume":"12","author":"Saborowski","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1126\/science.abj5104","article-title":"Oncometabolite d-2HG alters T cell metabolism to impair CD8+ T cell function","volume":"377","author":"Notarangelo","year":"2022","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ccr.2010.12.014","article-title":"Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of \u03b1-Ketoglutarate-Dependent Dioxygenases","volume":"19","author":"Xu","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/hep.32424","article-title":"Biology of IDH mutant cholangiocarcinoma","volume":"75","author":"Wu","year":"2022","journal-title":"Hepatology"},{"key":"ref_58","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_59","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":"2024","journal-title":"Hepatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1158\/2159-8290.CD-23-0282","article-title":"An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma","volume":"13","author":"Zhang","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lin, J., Sang, C., Xiang, B., Shen, X., Zhao, J., Xu, S., Pan, J., Lin, Y., Dong, L., and Chu, Q. (2026). Arachidonic Acid Metabolism in PMN-MDSCs Suppresses Antitumor Capacity of T cells in KRAS-Mutant Cholangiocarcinoma. Cancer Discov.","DOI":"10.1158\/2159-8290.CD-25-1844"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1186\/s12935-021-02081-w","article-title":"Relationship between PD-L1 expression, CD8+ T-cell infiltration and prognosis in intrahepatic cholangiocarcinoma patients","volume":"21","author":"Deng","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Xian, F., Ren, D., Bie, J., and Xu, G. (2023). Prognostic value of programmed cell death ligand 1 expression in patients with intrahepatic cholangiocarcinoma: A meta-analysis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1119168"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1084\/jem.2046fta","article-title":"CTLA-4: From conflict to clinic","volume":"204","author":"Bashyam","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2017-06-741033","article-title":"CTLA-4: A moving target in immunotherapy","volume":"131","author":"Rowshanravan","year":"2018","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Guo, X.-J., Lu, J.-C., Zeng, H.-Y., Zhou, R., Sun, Q.-M., Yang, G.-H., Pei, Y.-Z., Meng, X.-L., Shen, Y.-H., and Zhang, P.-F. (2021). CTLA-4 Synergizes With PD1\/PD-L1 in the Inhibitory Tumor Microenvironment of Intrahepatic Cholangiocarcinoma. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.705378"},{"key":"ref_67","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 Vallejo, J.G. (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_68","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13045-023-01499-1","article-title":"Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy","volume":"16","author":"Cai","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/bjc.2015.337","article-title":"Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer","volume":"113","author":"Goeppert","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.trecan.2016.12.003","article-title":"NLRC5\/CITA: A Key Player in Cancer Immune Surveillance","volume":"3","author":"Yoshihama","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5999","DOI":"10.1073\/pnas.1602069113","article-title":"NLRC5\/MHC class I transactivator is a target for immune evasion in cancer","volume":"113","author":"Yoshihama","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Taylor, B.C., and Balko, J.M. (2022). Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.844866"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1093\/carcin\/22.10.1615","article-title":"DNA hypermethylation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomas","volume":"22","author":"Nie","year":"2001","journal-title":"Carcinogenesis"},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/1097-0142(19920901)70:5<1057::AID-CNCR2820700508>3.0.CO;2-E","article-title":"Expression of HLA-DR in intrahepatic cholangiocarcinoma","volume":"70","author":"Torii","year":"1992","journal-title":"Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3558200","DOI":"10.1155\/2022\/3558200","article-title":"Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing","volume":"2022","author":"Bian","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41392-025-02347-z","article-title":"NADPH oxidase 1\/4 dual inhibition impairs transforming growth factor-beta protumorigenic effects in cholangiocarcinoma cancer-associated fibroblasts","volume":"10","author":"Amengual","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40659-015-0016-9","article-title":"TGF-\u03b21 expression is associated with invasion and metastasis of intrahepatic cholangiocarcinoma","volume":"48","author":"Chen","year":"2015","journal-title":"Biol. Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Liu, Z., Weng, S., Xu, H., Wang, L., Liu, L., Zhang, Y., Guo, C., Dang, Q., Xing, Z., and Lu, T. (2021). Computational Recognition and Clinical Verification of TGF-\u03b2-Derived miRNA Signature With Potential Implications in Prognosis and Immunotherapy of Intrahepatic Cholangiocarcinoma. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.757919"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Meireson, A., Devos, M., and Brochez, L. (2020). IDO Expression in Cancer: Different Compartment, Different Functionality?. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.531491"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Cao, L., Prithviraj, P., Shrestha, R., Sharma, R., Anaka, M., Bridle, K.R., Kannourakis, G., Crawford, D.H., and Jayachandran, A. (2021). Prognostic Role of Immune Checkpoint Regulators in Cholangiocarcinoma: A Pilot Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10102191"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Munir, S., Larsen, S.K., Iversen, T.Z., Donia, M., Klausen, T.W., Svane, I.M., Straten, P.T., and Andersen, M.H. (2012). Natural CD4+ T-Cell Responses against Indoleamine 2,3-Dioxygenase. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034568"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1016\/j.celrep.2016.10.079","article-title":"Stress Kinase GCN2 Controls the Proliferative Fitness and Trafficking of Cytotoxic T Cells Independent of Environmental Amino Acid Sensing","volume":"17","author":"Guo","year":"2016","journal-title":"Cell Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.4049\/jimmunol.0903670","article-title":"An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells","volume":"185","author":"Mezrich","year":"2010","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"117149","DOI":"10.1016\/j.celrep.2026.117149","article-title":"Subversion of kynurenine-induced AHR activation in CD8 T cells by kynureninase-expressing antigen-presenting cells","volume":"45","author":"Giacomantonio","year":"2026","journal-title":"Cell Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"eadi4191","DOI":"10.1126\/sciimmunol.adi4191","article-title":"A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression","volume":"9","author":"Plebanek","year":"2024","journal-title":"Sci. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41467-024-44795-1","article-title":"Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma","volume":"15","author":"Lu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/JCO.19.02105","article-title":"Efficacy of Pembrolizumab in Patients with Noncolorectal High Microsatellite Instability\/Mismatch Repair\u2013Deficient Cancer: Results From the Phase II KEYNOTE-158 Study","volume":"38","author":"Marabelle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1007\/s40265-014-0314-5","article-title":"Pembrolizumab: First Global Approval","volume":"74","author":"Poole","year":"2014","journal-title":"Drugs"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s40425-017-0242-5","article-title":"Evaluation of dosing strategy for pembrolizumab for oncology indications","volume":"5","author":"Freshwater","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e003091","DOI":"10.1136\/jitc-2021-003091","article-title":"Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: A pan-tumor retrospective analysis of participants with advanced solid tumors","volume":"10","author":"Cristescu","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_93","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_94","doi-asserted-by":"crossref","first-page":"644","DOI":"10.6004\/jnccn.2019.7304","article-title":"Prolonged Response to Anti\u2013PD-1 Antibody Therapy in Chemotherapy-Refractory Cholangiocarcinoma With High Tumor Mutational Burden","volume":"17","author":"Gbolahan","year":"2019","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_95","first-page":"325","article-title":"Nivolumab: An investigational agent for the treatment of biliary tract cancer","volume":"30","author":"Rizzo","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_96","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_97","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_98","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1080\/13543784.2021.1974838","article-title":"Atezolizumab: An investigational agent for the treatment of biliary tract cancer","volume":"30","author":"Hack","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"17588359211036544","DOI":"10.1177\/17588359211036544","article-title":"IMbrave 151: A randomized phase II trial of atezolizumab combined with bevacizumab and chemotherapy in patients with advanced biliary tract cancer","volume":"13","author":"Hack","year":"2021","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1200\/JCO.24.00337","article-title":"Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial","volume":"43","author":"Macarulla","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/j.jhep.2023.08.017","article-title":"Molecular-based targeted therapies in patients with hepatocellular carcinoma and hepato-cholangiocarcinoma refractory to atezolizumab\/bevacizumab","volume":"79","author":"Limousin","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e152670","DOI":"10.1172\/JCI152670","article-title":"Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers","volume":"131","author":"Yarchoan","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_103","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","volume":"6","author":"Klein","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1097\/HEP.0000000000000965","article-title":"Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2\/3 trial","volume":"81","author":"Oh","year":"2024","journal-title":"Hepatology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/HEP.0000000000000365","article-title":"Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced\/metastatic biliary tract cancers","volume":"78","author":"Yoo","year":"2023","journal-title":"Hepatology"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Teixeira, A.F., Ten Dijke, P., and Zhu, H.-J. (2020). On-Target Anti-TGF-\u03b2 Therapies Are Not Succeeding in Clinical Cancer Treatments: What Are Remaining Challenges?. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00605"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13045-021-01053-x","article-title":"Novel therapies emerging in oncology to target the TGF-\u03b2 pathway","volume":"14","author":"Kim","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.canlet.2013.12.018","article-title":"Attenuation of TGF-\u03b2 signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model","volume":"346","author":"Biswas","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S1470-2045(24)00082-2","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): Patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"25","author":"Burris","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00262-024-03842-y","article-title":"Exploring the impact of durvalumab on biliary tract cancer: Insights from real-world clinical data","volume":"73","author":"Reimann","year":"2024","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_111","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_112","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.jhep.2025.03.019","article-title":"Health-related quality of life in participants with advanced biliary tract cancer from the randomized phase III KEYNOTE-966 study","volume":"83","author":"Yoo","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3350\/cmh.2021.0287","article-title":"Intrahepatic cholangiocarcinoma: Tumour heterogeneity and its clinical relevance","volume":"28","author":"Komuta","year":"2022","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_114","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_115","doi-asserted-by":"crossref","first-page":"2101230","DOI":"10.1002\/advs.202101230","article-title":"IDH Mutation Subgroup Status Associates with Intratumor Heterogeneity and the Tumor Microenvironment in Intrahepatic Cholangiocarcinoma","volume":"8","author":"Xiang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41571-021-00521-0","article-title":"The implications of IDH mutations for cancer development and therapy","volume":"18","author":"Pirozzi","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s43018-024-00865-3","article-title":"Evolving cell states and oncogenic drivers during the progression of IDH-mutant gliomas","volume":"6","author":"Wu","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.trecan.2017.12.005","article-title":"Metabolism, Activity, and Targeting of D- and L-2-Hydroxyglutarates","volume":"4","author":"Ye","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_119","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":"Oncol."},{"key":"ref_120","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_121","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":"Signal Transduct. Target. Ther."},{"key":"ref_122","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_123","doi-asserted-by":"crossref","unstructured":"Garrido, F., Perea, F., Bernal, M., S\u00e1nchez-Palencia, A., Aptsiauri, N., and Ruiz-Cabello, F. (2017). The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture. Vaccines, 5.","DOI":"10.3390\/vaccines5010007"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1002\/hep.510300609","article-title":"Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: Its relationship with a new morphological classification of cholangiocarcinoma","volume":"30","author":"Higashi","year":"1999","journal-title":"Hepatology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4251\/wjgo.v7.i11.338","article-title":"Immunotherapeutic approaches in biliary tract carcinoma: Current status and emerging strategies","volume":"7","author":"Marks","year":"2015","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1097\/CJI.0b013e3181fb65b9","article-title":"Phase 1 Trial of Wilms Tumor 1 (WT1) Peptide Vaccine and Gemcitabine Combination Therapy in Patients with Advanced Pancreatic or Biliary Tract Cancer","volume":"34","author":"Kaida","year":"2011","journal-title":"J. Immunother."},{"key":"ref_127","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_128","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_129","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_130","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":"2011","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrc2355","article-title":"Adoptive cell transfer: A clinical path to effective cancer immunotherapy","volume":"8","author":"Rosenberg","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00595-006-3201-1","article-title":"Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis Successfully Treated by Immunotherapy with CD3-Activated T Cells and Dendritic Cells After Surgery: Report of a Case","volume":"36","author":"Higuchi","year":"2006","journal-title":"Surg. Today"},{"key":"ref_133","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_134","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":"2017","journal-title":"Protein Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"6276","DOI":"10.1038\/s41598-021-85747-9","article-title":"Anti-mucin 1 chimeric antigen receptor T cells for adoptive T cell therapy of cholangiocarcinoma","volume":"11","author":"Supimon","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1080\/07357900802189832","article-title":"Human Cytokine-Induced Killer Cells Specifically Infiltrated and Retarded the Growth of the Inoculated Human Cholangiocarcinoma Cells in SCID Mice","volume":"27","author":"Wongkajornsilp","year":"2009","journal-title":"Cancer Investig."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:58:51Z","timestamp":1783933131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":136,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146228"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146228","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]}}}