{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:49:57Z","timestamp":1793368197991,"version":"4.5.0"},"reference-count":197,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Biliary tract cancer, which includes intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, presents a significant clinical challenge because of its aggressive nature and limited therapeutic options. Although standard chemotherapy regimens, such as gemcitabine and cisplatin, are used, the prognosis for advanced biliary tract cancer patients remains poor due to the rapid development of resistance. Recently, advancements in immunotherapy, particularly immune checkpoint inhibitors, have shown promise. However, the response rate in patients with biliary tract cancer is still suboptimal primarily because of the highly immunosuppressive tumour microenvironment. This microenvironment includes a complex network of tumour-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, all of which contribute to immune evasion. In this review, we discuss the molecular mechanisms that drive biliary tract cancer, focusing on genetic alterations and the role of the TME in immune suppression. We also examine current combination strategies that integrate immune checkpoint inhibitors with chemotherapy and targeted therapies, which have demonstrated superior efficacy over monotherapy. Furthermore, we explore emerging therapeutic approaches, such as metabolic modulation, CAR-T-cell therapy, and mRNA vaccines, which are reshaping the treatment landscape. Finally, we highlight the need for personalized treatment strategies and the development of predictive biomarkers to guide therapy selection. Future research should focus on refining these combination therapies, optimizing patient selection, and validating biomarkers to improve clinical outcomes and survival in biliary tract cancer patients.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1651769","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:27:20Z","timestamp":1754630840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Jingnan","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00336-3","article-title":"Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study","volume":"22","author":"Javle","year":"2021","journal-title":"Lancet Oncol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1097\/HEP.0000000000001200","article-title":"International trends in biliary tract cancer-related mortality, 2000\u20132022: an observational study of the World Health Organization Mortality Database","volume":"10","author":"Vu","year":"2024","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","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":"B4","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/S1470-2045(21)00027-9","article-title":"Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial","volume":"22","author":"Lamarca","year":"2021","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","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":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12546","article-title":"Converting \u201ccold\u201d to \u201chot\u201d: epigenetics strategies to improve immune therapy effect by regulating tumor-associated immune suppressive cells","volume":"44","author":"Tang","year":"2024","journal-title":"Cancer Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202008386","article-title":"Electromagnetic nanomedicines for combinational cancer immunotherapy","volume":"60","author":"Li","year":"2021","journal-title":"Angewandte Chemie Int Edition"},{"key":"B8","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s12951-025-03170-y","article-title":"Co-delivery of axitinib and PD-L1 siRNA for the synergism of vascular normalization and immune checkpoint inhibition to boost anticancer immunity","volume":"23","author":"Liu","year":"2025","journal-title":"J Nanobiotechnol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"122766","DOI":"10.1016\/j.biomaterials.2024.122766","article-title":"Napabucasin deactivates STAT3 and promotes mitoxantrone-mediated cGAS-STING activation for hepatocellular carcinoma chemo-immunotherapy","volume":"313","author":"Wang","year":"2025","journal-title":"Biomaterials"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.4401","article-title":"Rationale for immune checkpoint inhibitors plus targeted therapy in metastatic melanoma: a review","volume":"6","author":"Dummer","year":"2020","journal-title":"JAMA Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002474","article-title":"Statin-mediated inhibition of RAS prenylation activates ER stress to enhance the immunogenicity of KRAS mutant cancer","volume":"9","author":"Nam","year":"2021","journal-title":"J ImmunoTherapy Cancer"},{"key":"B12","doi-asserted-by":"publisher","first-page":"102170","DOI":"10.1016\/j.ctrv.2021.102170","article-title":"Targeting FGFR inhibition in cholangiocarcinoma","volume":"95","author":"Goyal","year":"2021","journal-title":"Cancer Treat Rev"},{"key":"B13","doi-asserted-by":"publisher","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":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000664","article-title":"IL-8\u2013NF-\u03baB\u2013ALDH1A1 loop promotes the progression of intrahepatic cholangiocarcinoma","volume":"9","author":"Song","year":"2025","journal-title":"Hepatol Commun"},{"key":"B15","doi-asserted-by":"publisher","first-page":"22429","DOI":"10.1038\/s41598-022-26747-1","article-title":"Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma","volume":"12","author":"Rattanasinchai","year":"2022","journal-title":"Sci Rep"},{"key":"B16","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s13046-022-02340-2","article-title":"The role of tumor-infiltrating lymphocytes in cholangiocarcinoma","volume":"41","author":"Liu","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"101967","DOI":"10.1016\/j.tranon.2024.101967","article-title":"Pancreatobiliary reflux increases macrophage-secreted IL-8 and activates the PI3K\/NF\u03baB pathway to promote cholangiocarcinoma progression","volume":"45","author":"Wu","year":"2024","journal-title":"Trans Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.9840","article-title":"KRAS allelic variants in biliary tract cancers","volume":"7","author":"Moffat","year":"2024","journal-title":"JAMA Network Open"},{"key":"B19","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1038\/s41419-024-07191-7","article-title":"PD-L2 of tumor-derived exosomes mediates the immune escape of cancer cells via the impaired T cell function","volume":"15","author":"Liu","year":"2024","journal-title":"Cell Death Disease"},{"key":"B20","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1186\/s12957-022-02747-3","article-title":"Prognostic value of functional SMAD4 localization in extrahepatic bile duct cancer","volume":"20","author":"Takayama","year":"2022","journal-title":"World J Surg Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S474348","article-title":"Focusing on the immune cells: recent advances in immunotherapy for biliary tract cancer","volume":"16","author":"Ni","year":"2024","journal-title":"Cancer Manage Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2020-000682","article-title":"Molecular profile of BRCA-mutated biliary tract cancers","volume":"5","author":"Spizzo","year":"2020","journal-title":"Esmo Open"},{"key":"B23","doi-asserted-by":"publisher","first-page":"S125","DOI":"10.1016\/j.ejca.2023.04.012","article-title":"297P Real-life efficacy of immune checkpoint inhibitors in microsatellite unstable\/mismatch repair-deficient (dMMR\/MSI-H) biliary tract cancer (BTC)","volume":"35","author":"le Brun","year":"2024","journal-title":"Ann Oncol"},{"key":"B24","doi-asserted-by":"publisher","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":"2023","journal-title":"J hepatology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"9960","DOI":"10.1038\/s41467-024-54387-8","article-title":"Whole-exome sequencing reveals genomic landscape of intrahepatic cholangiocarcinoma and identifies SAV1 as a potential driver","volume":"15","author":"Zhou","year":"2024","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1159\/000534443","article-title":"Genetic\/epigenetic alteration and tumor immune microenvironment in intrahepatic cholangiocarcinoma: transforming the immune microenvironment with molecular-targeted agents","volume":"13","author":"Nishida","year":"2024","journal-title":"Liver cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.05.007","article-title":"NOTCH-YAP1\/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma","volume":"163","author":"Hu","year":"2022","journal-title":"Gastroenterology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2021.11.001","article-title":"Combination therapies for targeting FGFR2 fusions in cholangiocarcinoma","volume":"8","author":"Saborowski","year":"2022","journal-title":"Trends Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.02.045","article-title":"Refining classification of cholangiocarcinoma subtypes via proteogenomic integration reveals new therapeutic prospects","volume":"164","author":"Cho","year":"2023","journal-title":"Gastroenterology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13046-024-03030-x","article-title":"RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated \u03b2-catenin signaling in cholangiocarcinoma","volume":"43","author":"Chang","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"108170","DOI":"10.1016\/j.pharmthera.2022.108170","article-title":"Ivosidenib in IDH1-mutated cholangiocarcinoma: Clinical evaluation and future directions","volume":"237","author":"Lavacchi","year":"2022","journal-title":"Pharmacol Ther"},{"key":"B32","doi-asserted-by":"publisher","first-page":"100762","DOI":"10.1016\/j.jhepr.2023.100762","article-title":"Spatial immunophenotypes predict clinical outcome in intrahepatic cholangiocarcinoma","volume":"5","author":"Zhu","year":"2023","journal-title":"JHEP Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-025-03075-5","article-title":"Spatial omics technology potentially promotes the progress of tumor immunotherapy","author":"Lan","year":"","journal-title":"Br J cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4499","DOI":"10.3748\/wjg.v29.i29.4499","article-title":"Bioenergetic alteration in gastrointestinal cancers: the good, the bad and the ugly","volume":"29","author":"Chu","year":"2023","journal-title":"World J Gastroenterology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.696","article-title":"Spatial omics: Navigating to the golden era of cancer research","volume":"12","author":"Wu","year":"2022","journal-title":"Clin Trans Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70331","article-title":"Unravelling tumour spatiotemporal heterogeneity using spatial multimodal data","volume":"15","author":"Zuo","year":"2025","journal-title":"Clin Trans Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp5753","article-title":"CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes","volume":"10","author":"Wassing","year":"2024","journal-title":"Sci Adv"},{"key":"B38","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1186\/s13046-024-03188-4","article-title":"MBD2 regulates the progression and chemoresistance of cholangiocarcinoma through interaction with WDR5","volume":"43","author":"Wang","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001023","article-title":"Epigenetic heterogeneity hotspots in human liver disease progression","volume":"81","author":"Hlady","year":"2025","journal-title":"Hepatology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1002\/hep.32125","article-title":"Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile","volume":"75","author":"Vedeld","year":"2022","journal-title":"Hepatology"},{"key":"B41","doi-asserted-by":"publisher","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":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.10.020","article-title":"Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer","volume":"82","author":"Hwang","year":"2025","journal-title":"J Hepatology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3306","DOI":"10.1038\/s41467-023-39055-7","article-title":"A high-throughput test enables specific detection of hepatocellular carcinoma","volume":"14","author":"Cheishvili","year":"2023","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1105","article-title":"UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation","volume":"52","author":"Tiedemann","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/hep.32102","article-title":"Synergistic combination of cytotoxic chemotherapy and cyclin-dependent kinase 4\/6 inhibitors in biliary tract cancers","volume":"75","author":"Arora","year":"2022","journal-title":"Hepatology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31094","article-title":"Modulation of biliary cancer chemo-resistance through microRNA-mediated rewiring of the expansion of CD133+ cells","volume":"72","author":"Carotenuto","year":"2020","journal-title":"Hepatology"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31642","article-title":"Dual targeting of G9a and DNA methyltransferase-1 for the treatment of experimental cholangiocarcinoma","volume":"73","author":"Colyn","year":"2021","journal-title":"Hepatology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31585","article-title":"Epigenome-wide analysis of methylation changes in the sequence of gallstone disease, dysplasia, and gallbladder cancer","volume":"73","author":"Br\u00e4gelmann","year":"2021","journal-title":"Hepatology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13046-024-03036-5","article-title":"The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling","volume":"43","author":"Ma","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-1173","article-title":"Mapping of the T-cell landscape of biliary tract cancer unravels anatomic subtype-specific heterogeneity","volume":"85","author":"Nie","year":"2025","journal-title":"Cancer Res"},{"key":"B51","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41421-020-00188-4","article-title":"USP7 negatively controls global DNA methylation by attenuating ubiquitinated histone-dependent DNMT1 recruitment","volume":"6","author":"Li","year":"2020","journal-title":"Cell discovery"},{"key":"B52","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s13046-024-03070-3","article-title":"Unveiling the role of HP1\u03b1-HDAC1-STAT1 axis as a therapeutic target for HP1\u03b1-positive intrahepatic cholangiocarcinoma","volume":"43","author":"Xiong","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02576","article-title":"Precision medicine in biliary tract cancer","volume":"40","author":"Scott","year":"2022","journal-title":"J Clin Oncol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.743","article-title":"Feedback loop LINC00511\u2013YTHDF2\u2013SOX2 regulatory network drives cholangiocarcinoma progression and stemness","volume":"5","author":"Guan","year":"2024","journal-title":"MedComm"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003214","article-title":"Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes","volume":"9","author":"Chen","year":"2021","journal-title":"J Immunotherapy Cancer"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.12.006","article-title":"Progress and promises of epigenetic drugs and epigenetic diets in cancer prevention and therapy: A clinical update","volume":"83","author":"Mondal","year":"2022","journal-title":"Semin Cancer Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000437","article-title":"Bile exosomal miR-182\/183-5p increases cholangiocarcinoma stemness and progression by targeting HPGD and increasing PGE2 generation","volume":"79","author":"Shu","year":"2024","journal-title":"Hepatology"},{"key":"B58","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12951-023-01986-0","article-title":"UTX deletion promotes M2 macrophage polarization by epigenetically regulating endothelial cell-macrophage crosstalk after spinal cord injury","volume":"21","author":"Peng","year":"2023","journal-title":"J Nanobiotechnology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"6417","DOI":"10.1038\/s41467-024-50882-0","article-title":"Harnessing DNA replication stress to target RBM10 deficiency in lung adenocarcinoma","volume":"15","author":"Machour FE","year":"2024","journal-title":"Nat Commun"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.12.034","article-title":"Cancer-secreted exosomal miR-1468-5p promotes tumor immune escape via the immunosuppressive reprogramming of lymphatic vessels","volume":"29","author":"Zhou","year":"2021","journal-title":"Mol Ther"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32387","article-title":"Tumor-derived exosomes induce immunosuppressive macrophages to foster intrahepatic cholangiocarcinoma progression","volume":"76","author":"Luo","year":"2022","journal-title":"Hepatology"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1431598","article-title":"Inhibition of IL-10 and TGF-\u03b2 receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells","volume":"14","author":"Thepmalee","year":"2018","journal-title":"Hum Vaccines immunotherapeutics"},{"key":"B63","doi-asserted-by":"publisher","first-page":"106564","DOI":"10.1016\/j.phrs.2022.106564","article-title":"SHH\/GLI2-TGF-\u03b21 feedback loop between cancer cells and tumor-associated macrophages maintains epithelial-mesenchymal transition and endoplasmic reticulum homeostasis in cholangiocarcinoma","volume":"187","author":"Chen","year":"2023","journal-title":"Pharmacol Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00475","article-title":"Prostaglanin-E2 potentiates the suppressive functions of human mononuclear myeloid-derived suppressor cells and increases their capacity to expand IL-10-producing regulatory T cell subsets","volume":"10","author":"Tomi\u0107","year":"2019","journal-title":"Front Immunol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"110091","DOI":"10.1016\/j.intimp.2023.110091","article-title":"MUC1 induces the accumulation of Foxp3+ Treg cells in the tumor microenvironment to promote the growth and metastasis of cholangiocarcinoma through the EGFR\/PI3K\/Akt signaling pathway","volume":"118","author":"Zhang","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15307","article-title":"Targeting interleukin 6 signaling by monoclonal antibody siltuximab on cholangiocarcinoma","volume":"36","author":"Nguyen","year":"2021","journal-title":"J Gastroenterol hepatology"},{"key":"B67","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.3390\/cancers13092134","article-title":"Cancer-associated fibroblast-derived IL-6 determines unfavorable prognosis in cholangiocarcinoma by affecting autophagy-associated chemoresponse","volume":"13","author":"Thongchot","year":"2021","journal-title":"Cancers"},{"key":"B68","doi-asserted-by":"publisher","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 discovery"},{"key":"B69","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ejca.2017.11.024","article-title":"Circulating oncometabolite D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate dehydrogenase\u2013mutated intrahepatic cholangiocarcinomas","volume":"90","author":"Delahousse","year":"2018","journal-title":"Eur J Cancer"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00082","article-title":"The IDH1 mutation-induced oncometabolite, 2-hydroxyglutarate, may affect DNA methylation and expression of PD-L1 in gliomas","volume":"11","author":"Mu","year":"2018","journal-title":"Front Mol Neurosci"},{"key":"B71","doi-asserted-by":"publisher","first-page":"3093","DOI":"10.3390\/cells10113093","article-title":"Tumor lymphatic interactions induce CXCR2-CXCL5 axis and alter cellular metabolism and lymphangiogenic pathways to promote cholangiocarcinoma","volume":"10","author":"Roy","year":"2021","journal-title":"Cells"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2018.9358","article-title":"Serum vascular endothelial growth factor\u2212C levels predict lymph node metastasis and prognosis of patients with gallbladder cancer","volume":"16","author":"Jiang","year":"2018","journal-title":"Oncol letters"},{"key":"B73","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1186\/s13046-022-02536-6","article-title":"Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-\u03b2 inhibition","volume":"41","author":"Mancarella","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c00417","article-title":"Photothermal depletion of cancer-associated fibroblasts normalizes tumor stiffness in desmoplastic cholangiocarcinoma","volume":"14","author":"Nicol\u00e1s-Boluda","year":"2020","journal-title":"ACS nano"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1704","article-title":"Isolation of cancer-associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma","volume":"7","author":"Sha","year":"2018","journal-title":"Cancer Med"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.05.031","article-title":"Resveratrol interrupts the pro-invasive communication between cancer associated fibroblasts and cholangiocarcinoma cells","volume":"430","author":"Thongchot","year":"2018","journal-title":"Cancer letters"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13046-020-01742-4","article-title":"Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway","volume":"39","author":"Pan","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"key":"B78","doi-asserted-by":"publisher","first-page":"4187","DOI":"10.3390\/ijms23084187","article-title":"The tumor microenvironment drives intrahepatic cholangiocarcinoma progression","volume":"23","author":"Mancarella","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2017.1310842","article-title":"Role of the Notch signaling in cholangiocarcinoma","volume":"21","author":"Cigliano","year":"2017","journal-title":"Expert Opin Ther targets"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-020-01726-6","article-title":"Downregulation of tumor-derived exosomal miR-34c induces cancer-associated fibroblast activation to promote cholangiocarcinoma progress","volume":"21","author":"Qin","year":"2021","journal-title":"Cancer Cell Int"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12943-018-0760-x","article-title":"The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells","volume":"17","author":"Utaijaratrasmi","year":"2018","journal-title":"Mol Cancer"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00472","article-title":"The role of exosomal microRNA in cancer drug resistance","volume":"10","author":"Guo","year":"2020","journal-title":"Front Oncol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.3390\/biomedicines12102381","article-title":"Insights into CSF-1R expression in the tumor microenvironment","volume":"12","author":"Tomassetti","year":"2024","journal-title":"Biomedicines"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-0088","article-title":"Hypoxia stimulates PYGB enzymatic activity to promote glycogen metabolism and cholangiocarcinoma progression","volume":"84","author":"Pan","year":"2024","journal-title":"Cancer Res"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32344","article-title":"Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids","volume":"76","author":"Ruiz de Gauna","year":"2022","journal-title":"Hepatology"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.12.031","article-title":"Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma","volume":"74","author":"Raggi","year":"2021","journal-title":"J Hepatology"},{"key":"B87","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13045-022-01253-z","article-title":"Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses","volume":"15","author":"Xia","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.11.005","article-title":"Integrating cytotoxic, targeted and immune therapies for cholangiocarcinoma","volume":"78","author":"Merters","year":"2023","journal-title":"J hepatology"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00242-5","article-title":"Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study","volume":"24","author":"Harding","year":"2023","journal-title":"Lancet Oncol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0209","article-title":"Genetic screens identify a context-specific PI3K\/p27Kip1 node driving extrahepatic biliary cancer","volume":"11","author":"Falcomat\u00e0","year":"2021","journal-title":"Cancer discovery"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.11.033","article-title":"Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes","volume":"74","author":"Nepal","year":"2021","journal-title":"J hepatology"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.05.014","article-title":"Landmark survival analysis and impact of anatomic site of origin in prospective clinical trials of biliary tract cancer","volume":"73","author":"McNamara","year":"2020","journal-title":"J hepatology"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(21)00171-0","article-title":"Current and emerging therapies for advanced biliary tract cancers","volume":"6","author":"Kam","year":"2021","journal-title":"Lancet Gastroenterol hepatology"},{"key":"B94","doi-asserted-by":"publisher","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 hepatology"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-332429","article-title":"Glutamine metabolic competition drives immunosuppressive reprogramming of intratumour GPR109A+ myeloid cells to promote liver cancer progression","volume":"74","author":"Yang","year":"2025","journal-title":"Gut"},{"key":"B96","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"Brindley","year":"2021","journal-title":"Nat Rev Dis primers"},{"key":"B97","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1136\/gutjnl-2020-322983","article-title":"Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis","volume":"71","author":"Goeppert","year":"2022","journal-title":"Gut"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1643","article-title":"IDH1 inhibition reawakens the immune response against cholangiocarcinoma","volume":"12","author":"Zhu","year":"2022","journal-title":"Cancer discovery"},{"key":"B99","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13046-021-01890-1","article-title":"HMGA1-TRIP13 axis promotes stemness and epithelial mesenchymal transition of perihilar cholangiocarcinoma in a positive feedback loop dependent on c-Myc","volume":"40","author":"Li","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32258","article-title":"Liver transplantation for intrahepatic cholangiocarcinoma: ready for prime time","volume":"75","author":"Sapisochin","year":"2022","journal-title":"Hepatology"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000001540","article-title":"Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1\/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study","volume":"110","author":"Wang","year":"2024","journal-title":"Int J Surgery"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-0955","article-title":"Computational analysis of cholangiocarcinoma phosphoproteomes identifies patient-specific drug targets","volume":"81","author":"Khorsandi","year":"2021","journal-title":"Cancer Res"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.12.008","article-title":"CD34+ CLDN5+ tumor associated senescent endothelial cells through IGF2-IGF2R signaling increased cholangiocellular phenotype in hepatocellular carcinoma","author":"Zhu","year":"2024","journal-title":"J Advanced Res"},{"key":"B104","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s12943-024-02095-8","article-title":"Programmed death receptor (PD-) 1\/PD-ligand (L) 1 in urological cancers: the \u201call-around warrior\u201d in immunotherapy","volume":"23","author":"Liu","year":"2024","journal-title":"Mol cancer"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.7150\/thno.45777","article-title":"Reducing PD-L1 expression with a self-assembled nanodrug: an alternative to PD-L1 antibody for enhanced chemo-immunotherapy","volume":"11","author":"Cai","year":"2021","journal-title":"Theranostics"},{"key":"B106","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s13046-021-01987-7","article-title":"Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer","volume":"40","author":"Zhang","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"B107","doi-asserted-by":"publisher","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":"B108","doi-asserted-by":"publisher","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":"Piha-Paul","year":"2020","journal-title":"Int J cancer"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009565","article-title":"FXa-mediated PAR-2 promotes the efficacy of immunotherapy for hepatocellular carcinoma through immune escape and anoikis resistance by inducing PD-L1 transcription","volume":"12","author":"Li","year":"2024","journal-title":"J immunotherapy cancer"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001240","article-title":"Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial","volume":"8","author":"Chen","year":"2020","journal-title":"J immunotherapy cancer"},{"key":"B111","doi-asserted-by":"publisher","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":"B112","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1016\/j.immuni.2025.02.017","article-title":"Anti-vascular endothelial growth factor treatment potentiates immune checkpoint blockade through a BAFF-and IL-12-dependent reprogramming of the TME","volume":"58","author":"Benmebarek","year":"2025","journal-title":"Immunity"},{"key":"B113","doi-asserted-by":"publisher","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 Invest"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.146707","article-title":"Hedgehog-induced PD-L1 on tumor-associated macrophages is critical for suppression of tumor-infiltrating CD8+ T cell function","volume":"6","author":"Petty","year":"2021","journal-title":"JCI Insight"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0413-z","article-title":"Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors","volume":"17","author":"Galluzzi","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13045-024-01558-1","article-title":"Targeting FGFR for cancer therapy","volume":"17","author":"Zhang","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B117","doi-asserted-by":"publisher","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":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.12.011","article-title":"A model for decoding resistance in precision oncology: acquired resistance to FGFR inhibitors in cholangiocarcinoma","volume":"36","author":"Goyal","year":"2024","journal-title":"Ann Oncol"},{"key":"B119","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41698-022-00304-5","article-title":"Secondary IDH1 resistance mutations and oncogenic IDH2 mutations cause acquired resistance to ivosidenib in cholangiocarcinoma","volume":"6","author":"Cleary","year":"2022","journal-title":"NPJ Precis Oncol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"15421","DOI":"10.1038\/s41598-023-42083-4","article-title":"Real world evidence reveals improved survival outcomes in biliary tract cancer through molecular matched targeted treatment","volume":"13","author":"Doleschal","year":"2023","journal-title":"Sci Rep"},{"key":"B121","doi-asserted-by":"publisher","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 Invest"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101420","article-title":"PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer","volume":"5","author":"Wang","year":"2024","journal-title":"Cell Rep Med"},{"key":"B123","doi-asserted-by":"publisher","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 hepatology"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.07.015","article-title":"Modulating Treg stability to improve cancer immunotherapy","volume":"9","author":"Kang","year":"2023","journal-title":"Trends cancer"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2025.03.035","article-title":"Tumor-derived CD109 orchestrates reprogramming of tumor-associated macrophages to dampen immune response","author":"Cui","year":"2025","journal-title":"J Hepatol"},{"key":"B126","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13045-024-01544-7","article-title":"Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives","volume":"17","author":"Lin","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c03387","article-title":"Breaking tumor immunosuppressive network by regulating multiple nodes with triadic drug delivery nanoparticles","volume":"17","author":"Yan","year":"2023","journal-title":"ACS nano"},{"key":"B128","doi-asserted-by":"publisher","first-page":"2310163","DOI":"10.1002\/advs.202310163","article-title":"Metabolism\/immunity dual-regulation thermogels potentiating immunotherapy of glioblastoma through lactate-excretion inhibition and PD-1\/PD-L1 blockade","volume":"11","author":"Li","year":"2024","journal-title":"Advanced science"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01430-3","article-title":"CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions","volume":"24","author":"Liu","year":"2023","journal-title":"Nat Immunol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324109","article-title":"GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity","volume":"71","author":"Ruffolo","year":"2022","journal-title":"Gut"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003488","article-title":"Vectorized Treg-depleting \u03b1CTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject \u2018cold\u2019tumors","volume":"10","author":"Semmrich","year":"2022","journal-title":"J Immunotherapy Cancer"},{"key":"B132","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12943-025-02270-5","article-title":"Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines","volume":"24","author":"Maksymova","year":"2025","journal-title":"Mol Cancer"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1172\/JCI187024","article-title":"Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma","volume":"135","author":"Sun","year":"2025","journal-title":"J Clin Invest"},{"key":"B134","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12943-025-02258-1","article-title":"Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment","volume":"24","author":"Wan","year":"2025","journal-title":"Mol Cancer"},{"key":"B135","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13045-023-01498-2","article-title":"Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics","volume":"16","author":"Jin","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B136","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jare.2024.02.009","article-title":"Targeting lipid metabolism of macrophages: A new strategy for tumor therapy","volume":"68","author":"Shao","year":"2025","journal-title":"J Advanced Res"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.12.025","article-title":"Local glycolysis-modulating hydrogel microspheres for a combined anti-tumor and anti-metastasis strategy through metabolic trapping strategy","volume":"378","author":"Han","year":"2025","journal-title":"J Controlled Release"},{"key":"B138","doi-asserted-by":"publisher","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":"B139","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0428","article-title":"Senescence defines a distinct subset of myofibroblasts that orchestrates immunosuppression in pancreatic cancer","volume":"14","author":"Belle","year":"2024","journal-title":"Cancer discovery"},{"key":"B140","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1097\/HEP.0000000000000552","article-title":"PTPN9 dephosphorylates FGFR2pY656\/657 through interaction with ACAP1 and ameliorates pemigatinib effect in cholangiocarcinoma","volume":"79","author":"Zhao","year":"2024","journal-title":"Hepatology"},{"key":"B141","volume-title":"Futibatinib for intrahepatic cholangiocarcinoma","author":"Baker","year":"2023"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.3836","article-title":"Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial","volume":"7","author":"Zhu","year":"2021","journal-title":"JAMA Oncol"},{"key":"B143","doi-asserted-by":"publisher","first-page":"5517","DOI":"10.1158\/1538-7445.AM2022-5517","article-title":"Addition of PD-1 antibody camrelizumab overcame resistance to trastuzumab plus chemotherapy in a HER2-positive, metastatic gallbladder cancer patient","volume":"82","author":"Yan","year":"2022","journal-title":"Cancer Res"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.08.052","article-title":"Gemcitabine-loaded DSPE-PEG-PheoA liposome as a photomediated immune modulator for cholangiocarcinoma treatment","volume":"183","author":"Kim","year":"2018","journal-title":"Biomaterials"},{"key":"B145","doi-asserted-by":"publisher","first-page":"122189","DOI":"10.1016\/j.biomaterials.2023.122189","article-title":"Injectable cold atmospheric plasma-activated immunotherapeutic hydrogel for enhanced cancer treatment","volume":"300","author":"Fang","year":"2023","journal-title":"Biomaterials"},{"key":"B146","doi-asserted-by":"publisher","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 Immunotherapy Cancer"},{"key":"B147","doi-asserted-by":"publisher","first-page":"2207343","DOI":"10.1002\/adma.202207343","article-title":"Metabolic homeostasis-regulated nanoparticles for antibody-independent cancer radio-immunotherapy","volume":"34","author":"Shen","year":"2022","journal-title":"Advanced Materials"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202419033","article-title":"Glucose metabolism-targeted poly (amino acid) nanoformulation of oxaliplatin (IV)-aspirin prodrug for enhanced chemo-immunotherapy","volume":"2419033","author":"Yang","year":"2025","journal-title":"Advanced Materials"},{"key":"B149","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.1038\/s41467-021-23394-4","article-title":"Cell-free DNA captures tumor heterogeneity and driver alterations in rapid autopsies with pre-treated metastatic cancer","volume":"12","author":"Pereira","year":"2021","journal-title":"Nat Commun"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1142690","article-title":"Revisiting targeted therapy and immunotherapy for advanced cholangiocarcinoma","volume":"14","author":"Du","year":"2023","journal-title":"Front Immunol"},{"key":"B151","doi-asserted-by":"publisher","first-page":"1","DOI":"10.25163\/biosciences.515805","article-title":"Beyond chemotherapy: precision oncology and the shift toward non-toxic, adaptive cancer therapies","volume":"5","author":"Dickens","year":"2023","journal-title":"J Precis Biosciences"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-024-00869-z","article-title":"FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions","volume":"21","author":"Katoh","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"B153","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41392-020-00449-4","article-title":"Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy","volume":"6","author":"Tang","year":"2021","journal-title":"Signal transduction targeted Ther"},{"key":"B154","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s13046-025-03377-9","article-title":"Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy","volume":"44","author":"Yang","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"B155","doi-asserted-by":"publisher","first-page":"3911","DOI":"10.7150\/ijbs.93697","article-title":"Using Combination therapy to overcome diverse challenges of Immune Checkpoint Inhibitors treatment","volume":"20","author":"Birnboim-Perach","year":"2024","journal-title":"Int J Biol Sci"},{"key":"B156","doi-asserted-by":"publisher","first-page":"5841","DOI":"10.3390\/cancers15245841","article-title":"Challenges and future directions in the management of tumor mutational burden-high (TMB-H) advanced solid Malignancies","volume":"15","author":"Ahmed","year":"2023","journal-title":"Cancers"},{"key":"B157","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/mco2.6","article-title":"Metabolism in tumor microenvironment: Implications for cancer immunotherapy","volume":"1","author":"Shi","year":"2020","journal-title":"MedComm"},{"key":"B158","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s41467-017-02696-6","article-title":"Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGF\u03b2 enhance the efficacy of cancer immunotherapy","volume":"9","author":"Ravi","year":"2018","journal-title":"Nat Commun"},{"key":"B159","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.immuni.2017.12.004","article-title":"Paracrine Wnt5a-\u03b2-catenin signaling triggers a metabolic program that drives dendritic cell tolerization","volume":"48","author":"Zhao","year":"2018","journal-title":"Immunity"},{"key":"B160","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s41467-020-20723-x","article-title":"Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles","volume":"12","author":"Wei","year":"2021","journal-title":"Nat Commun"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0074-9","article-title":"Rheumatic immune-related adverse events from cancer immunotherapy","volume":"14","author":"Calabrese","year":"2018","journal-title":"Nat Rev Rheumatol"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00597-8","article-title":"Harnessing big data to characterize immune-related adverse events","volume":"19","author":"Jing","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B163","doi-asserted-by":"publisher","first-page":"6310","DOI":"10.1038\/s41598-025-91102-z","article-title":"Effects of immune related adverse events and corticosteroids on the outcome of patients treated with immune checkpoint inhibitors","volume":"15","author":"\u015een","year":"2025","journal-title":"Sci Rep"},{"key":"B164","doi-asserted-by":"publisher","first-page":"114028","DOI":"10.1016\/j.ejca.2024.114028","article-title":"Second-line therapies for steroid-refractory immune-related adverse events in patients treated with immune checkpoint inhibitors","volume":"203","author":"Ruf","year":"2024","journal-title":"Eur J Cancer"},{"key":"B165","doi-asserted-by":"publisher","first-page":"113313","DOI":"10.1016\/j.ejca.2023.113313","article-title":"Immunosuppressant mycophenolate mofetil for patients with steroid-refractory immune-related hepatitis induced by checkpoint inhibitors in oncology","volume":"193","author":"Alouani","year":"2023","journal-title":"Eur J Cancer"},{"key":"B166","doi-asserted-by":"publisher","first-page":"keaf356","DOI":"10.1136\/annrheumdis-2025-eular.B133","article-title":"The therapeutic potential for JAK inhibitors for immune-related adverse events from checkpoint inhibitors\u2013a review of the literature","author":"Nagra","year":"2025","journal-title":"Rheumatology"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.611012","article-title":"Comparative efficacy and safety of immunotherapy alone and in combination with chemotherapy for advanced non-small cell lung cancer","volume":"11","author":"Wang","year":"2021","journal-title":"Front Oncol"},{"key":"B168","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40364-021-00312-w","article-title":"Antiangiogenic therapy reverses the immunosuppressive breast cancer microenvironment","volume":"9","author":"Chen","year":"2021","journal-title":"biomark Res"},{"key":"B169","doi-asserted-by":"publisher","first-page":"e007236","DOI":"10.1136\/jitc-2023-007236","article-title":"T-cell receptor beta variable gene polymorphism predicts immune-related adverse events during checkpoint blockade immunotherapy","volume":"11","author":"Stephen","year":"2023","journal-title":"J immunotherapy cancer"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz116","article-title":"ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1\/PD-L1 expression and tumour mutational burden: a systematic review-based approach","volume":"30","author":"Luchini","year":"2019","journal-title":"Ann Oncol"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.3384","article-title":"Molecular determinants of response to anti\u2013programmed cell death (PD)-1 and anti\u2013programmed death-ligand 1 (PD-L1) blockade in patients with non\u2013small-cell lung cancer profiled with targeted next-generation sequencing","volume":"36","author":"Rizvi","year":"2018","journal-title":"J Clin Oncol"},{"key":"B172","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12943-023-01731-z","article-title":"Roles of cancer-associated fibroblasts (CAFs) in anti-PD-1\/PD-L1 immunotherapy for solid cancers","volume":"22","author":"Pei","year":"2023","journal-title":"Mol cancer"},{"key":"B173","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12943-024-01990-4","article-title":"Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer","volume":"23","author":"Kundu","year":"2024","journal-title":"Mol Cancer"},{"key":"B174","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.7150\/thno.24821","article-title":"Nano-delivery of fraxinellone remodels tumor microenvironment and facilitates therapeutic vaccination in desmoplastic melanoma","volume":"8","author":"Hou","year":"2018","journal-title":"Theranostics"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101170","article-title":"New systemic treatment paradigms in advanced biliary tract cancer and variations in patient access across Europe","volume":"50","author":"Rimassa","year":"2025","journal-title":"Lancet Regional Health\u2013Europe"},{"key":"B176","doi-asserted-by":"publisher","first-page":"114301","DOI":"10.1016\/j.addr.2022.114301","article-title":"Modulating tumor physical microenvironment for fueling CAR-T cell therapy","volume":"185","author":"Luo","year":"2022","journal-title":"Advanced Drug delivery Rev"},{"key":"B177","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1002\/cac2.12452","article-title":"Enhancement of CAR-T cell activity against cholangiocarcinoma by simultaneous knockdown of six inhibitory membrane proteins","volume":"43","author":"Qiao","year":"2023","journal-title":"Cancer Commun"},{"key":"B178","doi-asserted-by":"publisher","first-page":"e010581","DOI":"10.1136\/jitc-2024-010581","article-title":"XCL1-secreting CEA CAR-T cells enhance endogenous CD8+ T cell responses to tumor neoantigens to confer a long-term antitumor immunity","volume":"13","author":"Li","year":"2025","journal-title":"J Immunotherapy Cancer"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.12.004","article-title":"Boosting CAR-T cell therapy through vaccine synergy","volume":"46","author":"Li","year":"2024","journal-title":"Trends Pharmacol Sci"},{"key":"B180","doi-asserted-by":"publisher","first-page":"1","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"},{"key":"B181","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13046-019-1372-z","article-title":"Cytolytic activity correlates with the mutational burden and deregulated expression of immune checkpoints in colorectal cancer","volume":"38","author":"Zaravinos","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.03.012","article-title":"Expression of lymphocyte-activating gene 3 and T-cell immunoreceptor with immunoglobulin and ITIM domains in cutaneous melanoma and their correlation with programmed cell death 1 expression in tumor-infiltrating lymphocytes","volume":"81","author":"Lee","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"B183","doi-asserted-by":"publisher","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":"B184","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s13045-022-01352-x","article-title":"Elraglusib (9-ING-41), a selective small-molecule inhibitor of glycogen synthase kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3 and enhances CD8+ T cell cytolytic killing of melanoma cells","volume":"15","author":"Shaw","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adi7418","article-title":"LRIG1 engages ligand VISTA and impairs tumor-specific CD8+ T cell responses","volume":"9","author":"Ta","year":"2024","journal-title":"Sci Immunol"},{"key":"B186","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13045-020-00917-y","article-title":"VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy","volume":"13","author":"Huang","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B187","doi-asserted-by":"publisher","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","author":"Oh","year":"2025","journal-title":"J Hepatol"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.02.007","article-title":"Applying artificial intelligence for cancer immunotherapy","volume":"11","author":"Xu","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"B189","doi-asserted-by":"publisher","first-page":"74","DOI":"10.60087\/jaigs.v3i1.68","article-title":"Harnessing AI and gut microbiome research for precision health","volume":"3","author":"Saxena","year":"2024","journal-title":"J Artif Intell Gen Sci (JAIGS)"},{"key":"B190","doi-asserted-by":"publisher","first-page":"206","DOI":"10.3390\/molecules26010206","article-title":"The microbiome and its implications in cancer immunotherapy","volume":"26","author":"Choudhry","year":"2021","journal-title":"Molecules"},{"key":"B191","doi-asserted-by":"publisher","first-page":"4919","DOI":"10.3748\/wjg.v26.i33.4919","article-title":"Exploring the food-gut axis in immunotherapy response of cancer patients","volume":"26","author":"Russo","year":"2020","journal-title":"World J Gastroenterology"},{"key":"B192","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0327-3","article-title":"Gut microbiome, big data and machine learning to promote precision medicine for cancer","volume":"17","author":"Cammarota","year":"2020","journal-title":"Nat Rev Gastroenterol hepatology"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.4018\/979-8-3693-5787-3","article-title":"Innovations in precision medicine and genomics: IGI global","author":"Koumpouros","year":"2025"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30321-1","article-title":"Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial","volume":"21","author":"Subbiah","year":"2020","journal-title":"Lancet Oncol"},{"key":"B195","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31862","article-title":"Molecular characterization of biliary tract cancer predicts chemotherapy and programmed death 1\/programmed death-ligand 1 blockade responses","volume":"74","author":"Yoon","year":"2021","journal-title":"Hepatology"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101277","article-title":"Personalized drug screening in patient-derived organoids of biliary tract cancer and its clinical application","volume":"4","author":"Ren","year":"2023","journal-title":"Cell Rep Med"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101294","article-title":"The potential of patient-derived organoids in precision medicine of biliary tract cancer","volume":"4","author":"Y\u00e1\u00f1ez-Bartolom\u00e9","year":"2023","journal-title":"Cell Rep Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1651769\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:27:22Z","timestamp":1754630842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1651769\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":197,"alternative-id":["10.3389\/fimmu.2025.1651769"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1651769","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]},"article-number":"1651769"}}