Background: Cholangiocarcinoma (CCA) encompasses a heterogeneous group of malignant tumors with dismal prognosis and increasing incidence worldwide. Both late diagnosis due to the lack of early symptoms and the refractory nature of these tumors seriously compromise patients’ welfare and outcomes. Summary: During the last decade, immunotherapy and, more specifically, modulation of immune checkpoints-mediated signaling pathways have been under the spotlight in the field of oncology, emerging as a potential therapeutic approach for the treatment of several cancers, including CCA. Generally, high expression levels of immune checkpoints in patients with CCA have been associated with worse clinical outcomes, particularly with shorter overall survival and relapse-free survival. Thus, immune checkpoint inhibitors (ICIs), which mainly constitute different monoclonal antibodies, have been developed in order to hamper the immune checkpoint-mediated pathways. Interestingly, chemotherapy may increase the expression of immune checkpoints, while other therapeutic approaches such as ablative and targeted therapies may enhance their antitumor activity. In this sense, several clinical trials evaluated the safety and efficacy of ICIs for CCA, both as a monotherapy and in combination with other ICIs or loco-regional and systemic therapies. Additionally, many other clinical trials are currently ongoing and results are eagerly awaited. Here, we summarize the key aspects of immune checkpoint molecules as prognostic factors and therapeutic targets in CCA, highlighting the most recent advances in the field and future research directions. Key Messages: (1) Effective therapeutic approaches for CCA are urgently needed. (2) Expression levels of immune checkpoints in patients with CCA have been proposed to be related with clinical outcomes. (3) Combination of different ICIs may outperform the efficacy of ICI monotherapy for CCA treatment. (4) Recent studies point toward the combination of ICIs and other common therapies, especially chemotherapy, as a promising strategy for treatment of CCA patients.
Liver Cancer

中文翻译：

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免疫检查点抑制剂：胆管癌治疗的新兴基石？

背景：胆管癌 (CCA) 是一组异质性恶性肿瘤，在全球范围内预后不佳且发病率不断增加。由于缺乏早期症状而导致的晚期诊断和这些肿瘤的难治性都严重损害了患者的福利和结果。概括：在过去的十年中，免疫疗法，更具体地说，免疫检查点介导的信号通路的调节一直受到肿瘤学领域的关注，成为治疗包括 CCA 在内的多种癌症的潜在治疗方法。一般来说，CCA 患者免疫检查点的高表达水平与较差的临床结果相关，尤其是较短的总生存期和无复发生存期。因此，已经开发了主要构成不同单克隆抗体的免疫检查点抑制剂（ICI），以阻碍免疫检查点介导的途径。有趣的是，化学疗法可能会增加免疫检查点的表达，而其他治疗方法（如消融和靶向治疗）可能会增强其抗肿瘤活性。从这个意义上说，几项临床试验评估了 ICI 对 CCA 的安全性和有效性，无论是作为单一疗法还是与其他 ICI 或局部和全身疗法联合使用。此外，许多其他临床试验目前正在进行中，并热切期待结果。在这里，我们总结了免疫检查点分子作为 CCA 预后因素和治疗靶点的关键方面，重点介绍了该领域的最新进展和未来的研究方向。关键信息： (1) 迫切需要有效的 CCA 治疗方法。(2) 已提出CCA患者免疫检查点表达水平与临床结局相关。(3) 不同 ICI 的组合可能优于 ICI 单药治疗 CCA 的疗效。(4) 最近的研究表明，将 ICI 与其他常见疗法，尤其是化学疗法相结合，作为治疗 CCA 患者的一种有前景的策略。
肝癌