Fiste Oraianthi, Ntanasis-Stathopoulos Ioannis, Gavriatopoulou Maria, Liontos Michalis, Koutsoukos Konstantinos, Dimopoulos Meletios Athanasios, Zagouri Flora
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital 80 Vasilissis Sophias, 11528 Athens, Greece.
Vaccines (Basel). 2021 Apr 22;9(5):422. doi: 10.3390/vaccines9050422.
Biliary tract cancer, and intrahepatic cholangiocarcinoma (iCC) in particular, represents a rather uncommon, highly aggressive malignancy with unfavorable prognosis. Therapeutic options remain scarce, with platinum-based chemotherapy is being considered as the gold standard for the management of advanced disease. Comprehensive molecular profiling of tumor tissue biopsies, utilizing multi-omics approaches, enabled the identification of iCC's intratumor heterogeneity and paved the way for the introduction of novel targeted therapies under the scope of precision medicine. Yet, the unmet need for optimal care of patients with chemo-refractory disease or without targetable mutations still exists. Immunotherapy has provided a paradigm shift in cancer care over the past decade. Currently, immunotherapeutic strategies for the management of iCC are under intense research. Intrinsic factors of the tumor, including programmed death-ligand 1 (PD-L1) expression and mismatch repair (MMR) status, are simply the tip of the proverbial iceberg with regard to resistance to immunotherapy. Acknowledging the significance of the tumor microenvironment (TME) in both cancer growth and drug response, we broadly discuss about its diverse immune components. We further review the emerging role of immunotherapy in this rare disease, summarizing the results of completed and ongoing phase I-III clinical trials, expounding current challenges and future directions.
胆道癌，尤其是肝内胆管癌（iCC），是一种较为罕见、侵袭性很强且预后不良的恶性肿瘤。治疗选择仍然有限，铂类化疗被视为晚期疾病治疗的金标准。利用多组学方法对肿瘤组织活检进行全面的分子分析，能够识别iCC的肿瘤内异质性，并为在精准医学范围内引入新型靶向治疗铺平了道路。然而，对于化疗难治性疾病或无靶向突变患者的最佳治疗需求仍未得到满足。在过去十年中，免疫疗法在癌症治疗方面带来了范式转变。目前，针对iCC治疗的免疫治疗策略正在深入研究中。肿瘤的内在因素，包括程序性死亡配体1（PD-L1）表达和错配修复（MMR）状态，在免疫治疗耐药方面只是冰山一角。认识到肿瘤微环境（TME）在癌症生长和药物反应中的重要性，我们广泛讨论其多样的免疫成分。我们进一步回顾免疫疗法在这种罕见疾病中的新兴作用，总结已完成和正在进行的I-III期临床试验结果，阐述当前挑战和未来方向。
