Banales, J. M. et al. Cholangiocarcinoma: state-of-the-art knowledge and challenges. Liver Int. 39, 5–6 (2019).

Article  PubMed  Google Scholar 

Brindley, P. J. et al. Cholangiocarcinoma. Nat. Rev. Dis. Prim. 7, 65 (2021).

Article  PubMed  Google Scholar 

Banales, J. M. et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat. Rev. Gastroenterol. Hepatol. 17, 557–588 (2020).

Article  PubMed Central  PubMed  Google Scholar 

Rizvi, S., Khan, S. A., Hallemeier, C. L., Kelley, R. K. & Gores, G. J. Cholangiocarcinoma– evolving concepts and therapeutic strategies. Nat. Rev. Clin. Oncol. 15, 95–111 (2018).

Article  CAS  PubMed  Google Scholar 

Affo, S. et al. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell 39, 883 (2021).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Yang, J. D. et al. DNA methylation markers for detection of cholangiocarcinoma: discovery, validation, and clinical testing in biliary brushings and plasma. Hepatol. Commun. 5, 1448–1459 (2021).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Zill, O. A. et al. Cell-free DNA next-generation sequencing in pancreatobiliary carcinomas. Cancer Discov. 5, 1040–1048 (2015).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Wu, M. J., Shi, L., Merritt, J., Zhu, A. X. & Bardeesy, N. Biology of IDH mutant cholangiocarcinoma. Hepatology 75, 1322–1337 (2022).

Article  CAS  PubMed  Google Scholar 

Kelley, R. K., Bridgewater, J., Gores, G. J. & Zhu, A. X. Systemic therapies for intrahepatic cholangiocarcinoma. J. Hepatol. 72, 353–363 (2020).

Article  CAS  PubMed  Google Scholar 

Abou-Alfa, G. K. et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 21, 671–684 (2020).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Javle, M. et al. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol. Hepatol. 6, 803–815 (2021).

Article  PubMed  Google Scholar 

Goyal, L. et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N. Engl. J. Med. 388, 228–239 (2023).

Article  CAS  PubMed  Google Scholar 

US Food and Drug Administration. FDA grants accelerated approval to pemigatinib for cholangiocarcinoma with an FGFR2 rearrangement or fusion. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement-or-fusion (2020).

US Food and Drug Administration. FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma (2021).

US Food and Drug Administration. FDA grants accelerated approval to futibatinib for cholangiocarcinoma. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-futibatinib-cholangiocarcinoma (2022).

Abou-Alfa, G. K. et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 21, 796–807 (2020).

Article  CAS  PubMed Central  PubMed  Google Scholar 

US Food and Drug Administration. FDA approves ivosidenib for advanced or metastatic cholangiocarcinoma. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-advanced-or-metastatic-cholangiocarcinoma (2022).

Gravely, A. K., Vibert, E. & Sapisochin, G. Surgical treatment of intrahepatic cholangiocarcinoma. J. Hepatol. https://doi.org/10.1016/j.jhep.2022.01.004 (2022).

Article  PubMed  Google Scholar 

Wang, J., Loeuillard, E., Gores, G. J. & Ilyas, S. I. Cholangiocarcinoma: what are the most valuable therapeutic targets – cancer-associated fibroblasts, immune cells, or beyond T cells? Expert. Opin. Ther. Targets 25, 835–845 (2021).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Loeuillard, E. et al. Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma. J. Clin. Invest. 130, 5380–5396 (2020).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Ruffolo, L. I. et al. GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity. Gut 71, 1386–1398 (2022).

Article  CAS  PubMed  Google Scholar 

Zhang, Q. et al. Gut microbiome directs hepatocytes to recruit MDSCs and promote cholangiocarcinoma. Cancer Discov. 11, 1248–1267 (2021).

Article  CAS  PubMed  Google Scholar 

Gani, F. et al. Program death 1 immune checkpoint and tumor microenvironment: implications for patients with intrahepatic cholangiocarcinoma. Ann. Surg. Oncol. 23, 2610–2617 (2016).

Article  PubMed  Google Scholar 

Zhou, G. et al. Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules. J. Hepatol. 71, 753–762 (2019).

Article  PubMed  Google Scholar 

Ghidini, M. et al. Characterisation of the immune-related transcriptome in resected biliary tract cancers. Eur. J. Cancer 86, 158–165 (2017).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Ma, L. et al. Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell 36, 418–430.e6 (2019).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Fabris, L., Sato, K., Alpini, G. & Strazzabosco, M. The tumor microenvironment in cholangiocarcinoma progression. Hepatology 73, 75–85 (2021).

Article  PubMed  Google Scholar 

Piha-Paul, S. A. et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: results from the KEYNOTE-158 and KEYNOTE-028 studies. Int. J. Cancer 147, 2190–2198 (2020).

Article  CAS  PubMed  Google Scholar 

Buettner, S. et al. The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma. Surgery 164, 411–418 (2018).

Article  PubMed  Google Scholar 

Peng, D. et al. Lymphocyte to monocyte ratio predicts resectability and early recurrence of Bismuth-Corlette type IV hilar cholangiocarcinoma. J. Gastrointest. Surg. 24, 330–340 (2020).

Article  PubMed  Google Scholar 

Tsilimigras, D. I. et al. The systemic immune-inflammation index predicts prognosis in intrahepatic cholangiocarcinoma: an international multi-institutional analysis. HPB 22, 1667–1674 (2020).

Article  PubMed  Google Scholar 

Sun, D. et al. CD86+/CD206+ tumor-associated macrophages predict prognosis of patients with intrahepatic cholangiocarcinoma. PeerJ 8, e8458 (2020).

Article  PubMed Central  PubMed  Google Scholar 

Yuan, D. et al. Kupffer cell-derived TNF triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS. Cancer Cell 31, 771–789.e6 (2017).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Boulter, L. et al. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J. Clin. Invest. 125, 1269–1285 (2015).

Article  PubMed Central  PubMed  Google Scholar 

Dwyer, B. J. et al. TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression. J. Hepatol. 74, 860–872 (2021).

Article  CAS  PubMed  Google Scholar 

Veglia, F., Perego, M. & Gabrilovich, D. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19, 108–119 (2018).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Xu, X. D. et al. Circulating myeloid-derived suppressor cells in patients with pancreatic cancer. Hepatobiliary Pancreat. Dis. Int. 15, 99–105 (2016).

Article  PubMed  Google Scholar 

Meyer, C. et al. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol. Immunother. 63, 247–257 (2014).

Article  CAS  PubMed  Google Scholar 

Song, G. et al. Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma. Nat. Commun. 13, 1642 (2022).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Bao, X. et al. Molecular subgroups of intrahepatic cholangiocarcinoma discovered by single-cell RNA sequencing-assisted multiomics analysis. Cancer Immunol. Res. 10, 811–828 (2022).

Article  CAS  PubMed