目前治疗胃肠道肿瘤的免疫治疗方法综述

Arushi Ramaka, Arvind Rajan, Ashwin Somasundaram
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引用次数: 0

摘要

胃肠道(GI)癌症占全球癌症病例和死亡的很大比例,并提出了重大的治疗挑战。免疫疗法,特别是免疫检查点抑制剂(ICIs),已经改变了治疗前景,并为各种胃肠道恶性肿瘤患者提供了改善的结果。对于食管癌,CheckMate 577、KEYNOTE 590、811和MATTERHORN等试验都证明了使用ICIs可以改善疗效。胰腺癌的特点是其免疫“冷”微环境,对免疫治疗的反应有限。然而,将免疫检查点抑制剂与化疗相结合的策略已经显示出一些早期结果。在结直肠癌中,微卫星不稳定-高/缺陷错配修复(MSI-H/dMMR)肿瘤对ICIs表现出强烈的反应,而正在进行的试验旨在改进微卫星稳定(MSS)病例的治疗方法。对于肝细胞癌(HCC),免疫联合治疗因其优于传统化疗而被视为一线治疗。胆管癌(CCA)缺乏术前肿瘤减少选择和新辅助治疗,但TOPAZ-1的结果显示,杜伐单抗、吉西他滨和顺铂联合治疗可提高晚期患者的总生存率。最后,免疫疗法正在成为晚期肛门癌的可行选择,试验探索检查点抑制剂和过继细胞疗法。尽管取得了进展,但肿瘤异质性和免疫抑制微环境等挑战需要持续研究以优化免疫治疗策略。免疫疗法已经彻底改变了胃肠道癌症的治疗,免疫检查点抑制剂在食管癌、结直肠癌和肝胆癌中显示出前景。然而,包括肿瘤异质性和免疫抑制微环境在内的挑战仍然存在。本文强调了在多种胃肠道恶性肿瘤中整合免疫治疗的进展、局限性和未来策略,强调需要创新方法来优化结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An overview of current immunotherapy approaches for treating gastrointestinal cancers
Gastrointestinal (GI) cancers, account for a substantial proportion of global cancer cases and deaths, and present significant therapeutic challenges. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has transformed the treatment landscape, and offered improved outcomes for patients presenting with various gastrointestinal malignancies. For esophageal cancer, trials like CheckMate 577, KEYNOTE 590, 811, and MATTERHORN have demonstrated improved benefit with ICIs. Pancreatic cancer, characterized by its immunologically "cold" microenvironment, has shown limited response to immunotherapy. However, strategies that combine immune checkpoint inhibitors with chemotherapy have shown some early results. In colorectal cancer, microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) tumors exhibit strong responses to ICIs, while ongoing trials aim to refine treatment for microsatellite-stable (MSS) cases. For hepatocellular carcinoma (HCC), immunotherapy combinations are regarded as a first-line treatment due to its efficacy over traditional chemotherapy. Cholangiocarcinoma (CCA) lacks pre-surgical tumor reduction options and neoadjuvant therapies, but the results of TOPAZ-1 showed that a combination of durvalumab, gemcitabine, and cisplatin improved overall survival in the advanced setting. Lastly, immunotherapy is emerging as a viable option for advanced forms of anal cancer, with trials exploring checkpoint inhibitors and adoptive cell therapies. Despite the progress, challenges such as tumor heterogeneity and immunosuppressive microenvironments necessitate ongoing research to optimize immunotherapeutic strategies.

Synopsis

Immunotherapy has revolutionized gastrointestinal cancer treatment, with immune checkpoint inhibitors showing promise in esophageal, colorectal, and hepatobiliary cancers. However, challenges including tumor heterogeneity and immunosuppressive microenvironments persist. This manuscript highlights advancements, limitations, and future strategies in integrating immunotherapy across diverse gastrointestinal malignancies, emphasizing the need for innovative approaches to optimize outcomes.
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