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肠道微生物群重塑肿瘤微环境并影响结直肠癌免疫治疗的疗效。

Gut Microbiota Reshapes the Tumor Microenvironment and Affects the Efficacy of Colorectal Cancer Immunotherapy.

作者信息

Wang Fayuan, Chen Weidong, Jia Yingtian, He Tao, Wu Siyi, Xiang Jiahui, Chen Rui, Jiang Qingfeng, Yu Tengjiang, Lan Yong, Li Wusheng, Ma Liang, He Ping, Li Shichao

机构信息

The Anorectal Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou City, Sichuan Province, China.

College of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou City, Sichuan Province, China.

出版信息

Cancer Med. 2025 Jun;14(12):e70994. doi: 10.1002/cam4.70994.

Abstract

BACKGROUND

Colorectal cancer (CRC) is among the most prevalent malignant tumors in the digestive system and is the third leading cause of cancer-related mortality. In recent years, immunotherapy has markedly enhanced the objective response and survival rates for CRC patients. However, the therapeutic efficacy of immunotherapy remains insufficient for the majority of proficient mismatch repair (pMMR) CRC patients, with 20% to 30% of deficient mismatch repair (dMMR) patients demonstrating poor responses or developing drug resistance. Increasing evidence underscores the critical role of intestinal microorganisms in modulating the effectiveness of immunotherapy, particularly in regulating the tumor microenvironment (TME).

METHODS

This review investigates the differences in intestinal microbiota and TME between dMMR and pMMR CRC. It explores how intestinal microbial communities influence TME components, including immune cells, macrophages, and fibroblasts, thereby impacting the response to immunotherapy.

CONCLUSION

Intestinal microorganisms play a critical role in the effectiveness of immunotherapy. Variations in intestinal microbiota and the TME among patients with different mismatch repair deficiencies can significantly influence the efficacy of immune checkpoint inhibitors. Modulating the intestinal microbiota has the potential to enhance the therapeutic response of CRC to immunotherapy.

摘要

背景

结直肠癌(CRC)是消化系统中最常见的恶性肿瘤之一,是癌症相关死亡的第三大主要原因。近年来,免疫疗法显著提高了CRC患者的客观缓解率和生存率。然而,对于大多数错配修复功能正常(pMMR)的CRC患者,免疫疗法的治疗效果仍然不足,20%至30%的错配修复缺陷(dMMR)患者表现出不良反应或产生耐药性。越来越多的证据强调肠道微生物群在调节免疫疗法有效性方面的关键作用,特别是在调节肿瘤微环境(TME)方面。

方法

本综述研究了dMMR和pMMR CRC患者肠道微生物群和TME的差异。探讨肠道微生物群落如何影响TME成分,包括免疫细胞、巨噬细胞和成纤维细胞,从而影响对免疫疗法的反应。

结论

肠道微生物群在免疫疗法的有效性中起关键作用。不同错配修复缺陷患者的肠道微生物群和TME差异可显著影响免疫检查点抑制剂的疗效。调节肠道微生物群有可能增强CRC对免疫疗法的治疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/141d/12175482/250fccfd07d7/CAM4-14-e70994-g004.jpg

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