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治疗胆管癌冷肿瘤的策略:核心概念和未来方向。

Strategies for treating the cold tumors of cholangiocarcinoma: core concepts and future directions.

机构信息

Department of Hepatobiliary Vascular Surgery, Chengdu Seventh People's Hospital, Chengdu, 610041, Sichuan, China.

出版信息

Clin Exp Med. 2024 Aug 14;24(1):193. doi: 10.1007/s10238-024-01460-7.

Abstract

Cholangiocarcinoma (CCA) is a rare type of digestive tract cancer originating from the epithelial cells of the liver and biliary tract. Current treatment modalities for CCA, such as chemotherapy and radiation therapy, have demonstrated limited efficacy in enhancing survival rates. Despite the revolutionary potential of immunotherapy in cancer management, its application in CCA remains restricted due to the minimal infiltration of immune cells in these tumors, rendering them cold and unresponsive to immune checkpoint inhibitors (ICIs). Cancer cells within cold tumors deploy various mechanisms for evading immune attack, thus impeding clinical management. Recently, combination immunotherapy has become increasingly essential to comprehend the mechanisms underlying cold tumors to enhance a deficient antitumor immune response. Therefore, a thorough understanding of the knowledge on the combination immunotherapy of cold CCA is imperative to leverage the benefits of immunotherapy in treating patients. Moreover, gut microbiota plays an essential role in the immunotherapeutic responses in CCA. In this review, we summarize the current concepts of immunotherapy in CCA and clarify the intricate dynamics within the tumor immune microenvironment (TIME) of CCA. We also delve into the evasion mechanisms employed by CCA tumors against the anti-tumor immune responses. The context of combination immunotherapies in igniting cold tumors of CCA and the critical function of gut microbiota in prompting immune responses have also been annotated. Furthermore, we have proposed future directions in the realm of CCA immunotherapy, aiming to improve the clinical prognosis of CCA patients.

摘要

胆管癌(CCA)是一种罕见的消化道癌症,起源于肝脏和胆道的上皮细胞。目前治疗 CCA 的方法,如化疗和放疗,已证明在提高生存率方面效果有限。尽管免疫疗法在癌症管理方面具有革命性的潜力,但由于这些肿瘤中免疫细胞的浸润程度较低,使它们成为冷肿瘤,对免疫检查点抑制剂(ICIs)无反应,因此其在 CCA 中的应用受到限制。冷肿瘤中的癌细胞会利用各种机制来逃避免疫攻击,从而阻碍临床管理。最近,联合免疫疗法对于理解冷肿瘤的机制以增强缺乏的抗肿瘤免疫反应变得越来越重要。因此,深入了解冷 CCA 的联合免疫疗法的相关知识对于利用免疫疗法治疗患者的益处至关重要。此外,肠道微生物群在 CCA 的免疫治疗反应中起着重要作用。在这篇综述中,我们总结了 CCA 免疫疗法的当前概念,并阐明了 CCA 肿瘤免疫微环境(TIME)中的复杂动态。我们还深入研究了 CCA 肿瘤对抗抗肿瘤免疫反应所采用的逃逸机制。我们还注释了联合免疫疗法在激发 CCA 的冷肿瘤和肠道微生物群在引发免疫反应方面的关键作用。此外,我们还提出了 CCA 免疫疗法领域的未来发展方向,旨在改善 CCA 患者的临床预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0186/11324771/3e2db0c61c78/10238_2024_1460_Fig1_HTML.jpg

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