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肿瘤免疫学的范式转变:Th17 细胞与 TGFβ在肠道癌症发生中的作用

英文原题:A Paradigm Shift in Tumor Immunology: Th17 Cells and TGFβ in Intestinal Cancer Initiation.

查看英文原题

A Paradigm Shift in Tumor Immunology: Th17 Cells and TGFβ in Intestinal Cancer Initiation.

PubMed 2024/12/02(内容时间) Cancer Res Q1 · IF 22.6(JCR 2025)

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中文摘要

癌症仍然是现代医学中最复杂的挑战之一,免疫反应与肿瘤发展之间存在错综复杂的关系。本文评述了Fesneau及其同事发表在Nature Immunology上的一项开创性研究。这项优雅的工作探索了慢性炎症与癌症之间的联系,尤其聚焦于参与肠癌发生的Th17细胞。Th17细胞以其在免疫中的双重作用而闻名,根据其所处环境的不同,既可促进也可抑制肿瘤生长。

该研究揭示,当TGFβ信号受损时,一个来源于IL17产生细胞的特定Th17细胞亚群可转变为致瘤状态。令人惊讶的是,TGFβ作为一个关键调控因子,通过阻止Th17细胞变为致瘤性,维持免疫耐受与肿瘤发生之间的平衡。这项研究凸显了靶向TGFβ信号通路的治疗干预在慢性炎症条件下预防癌症发生的潜力。这些发现对改善癌症免疫治疗具有临床意义,包括免疫检查点抑制剂和过继性T细胞疗法,通过增强治疗疗效并降低致瘤性转化风险。

总体而言,这项研究为炎症与癌症之间的关联机制提供了见解,为在癌症治疗中利用免疫力的创新策略铺平了道路。

展开英文摘要原文

Cancer remains one of the most complex challenges in modern medicine, with intricate relationships between immune responses and tumor development. This article examines a groundbreaking study by Fesneau and colleagues, published in Nature Immunology. This elegant body of work explores the link between chronic inflammation and cancer, particularly focusing on Th17 cells involved in intestinal cancer initiation. Th17 cells, known for their dual roles in immunity, can promote or inhibit tumor growth depending on their environment.

This study reveals that a specific subset of Th17 cells, derived from IL17-producing cells, can transition to a tumorigenic state when TGFβ signaling is impaired. Surprisingly, TGFβ acts as a crucial regulatory factor, maintaining the balance between immune tolerance and tumorigenesis by preventing Th17 cells from becoming tumorigenic.

This research highlights the potential for therapeutic interventions targeting TGFβ signaling to prevent cancer initiation under chronic inflammatory conditions. The findings have clinical implications for improving cancer immunotherapies, including immune checkpoint inhibitors and adoptive T-cell therapies, by enhancing the efficacy of treatments and mitigating the risk of tumorigenic transformations.

Overall, this study provides insights into the mechanisms linking inflammation and cancer, paving the way for innovative strategies to harness the immunity in cancer treatment.

论文信息

作者
Wyatt MM、Paulos CM
单位
Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute of Emory University, Atlanta, Georgia.United States
期刊
Cancer research2024 Dec 2
原文标识
PubMed 39292821 · DOI 10.1158/0008-5472.CAN-24-3361