《生命科学》 2026, 38(4): 667-676
CD4+ T细胞在结直肠肿瘤中的作用及靶向CD4+ T细胞的抗肿瘤策略研究进展
摘 要：
CD4+ T细胞在结直肠癌免疫微环境中发挥双重调控作用，既可促进抗肿瘤免疫，也可参与免疫抑制，是决定免疫治疗效果的关键因素。本文系统综述了结直肠癌中CD4+ T细胞各亚群（包括Th1、Th2、Th9、Th17、Treg、Tfh）的分化特征、调控机制及其在肿瘤免疫中的复杂功能。Th1和Tfh细胞通过分泌IFN-γ、IL-21等细胞因子，促进CD8+T细胞和B细胞功能，增强抗肿瘤反应，与患者良好预后及免疫检查点抑制剂敏感性密切相关。而Th2、Th17及Treg细胞在特定微环境中表现出促肿瘤特性，如诱导免疫抑制、促进血管生成和上皮-间质转化，与微卫星稳定（MSS）型结直肠癌患者免疫耐药性相关。本文进一步总结了CD4+ T细胞在免疫检查点阻断、癌症疫苗和CAR-T细胞疗法中的作用机制与临床应用进展。例如，纳武利尤单抗联合伊匹木单抗在微卫星高度不稳定（MSI-H）型CRC中疗效显著；个体化新抗原疫苗与mRNA疫苗展示出激活CD4+ T细胞辅助功能的潜力；在CAR-T细胞疗法中，CD4+ T细胞可增强疗效并延长免疫应答持续时间。尽管取得重要进展，MSS型CRC对免疫治疗响应有限、CD4+ T细胞异质性高、联合疗法的安全性与疗效平衡等问题仍待解决。未来应聚焦于精准调控CD4+ T细胞分化、逆转免疫抵抗、优化工程化T细胞设计，并加强临床转化研究，以实现从“认识微环境”到“重塑微环境”的跨越，为结直肠癌患者提供更有效的免疫治疗策略。
通讯作者：马 建 , Email:jma@hrbmu.edu.cn
Abstract:
CD4+ T cells exert dual regulatory roles in the colorectal cancer (CRC) immune microenvironment, capable of promoting anti-tumor immunity while also contributing to immunosuppression, making them critical determinants of immunotherapy efficacy. This review systematically summarizes the differentiation characteristics, regulatory mechanisms, and complex functions of CD4+ T cell subsets in CRC, including Th1, Th2, Th9, Th17, Treg, and Tfh cells. Th1 and Tfh cells promote CD8+ T cell and B cell functions by secreting cytokines such as IFN-γ and IL-21, thereby enhancing anti-tumor responses, which are closely associated with favorable patient prognosis and sensitivity to immune checkpoint inhibitors. In contrast, Th2, Th17, and Treg cells exhibit pro-tumor properties in specific microenvironments, such as inducing immunosuppression, promoting angiogenesis, and facilitating epithelial-mesenchymal transition, correlating with immune resistance in microsatellite stable (MSS) CRC patients. This review further summarizes the mechanisms and clinical application progress of CD4+ T cells in immune checkpoint blockade, cancer vaccines, and CAR-T cell therapy. For instance, the combination of nivolumab and ipilimumab has shown significant efficacy in MSI-H CRC; personalized neoantigen vaccines and mRNA vaccines demonstrate the potential to activate the helper functions of CD4+ T cells; in CAR-T cell therapy, CD4+ T cells can enhance therapeutic efficacy and prolong the duration of immune responses. Despite important advances, challenges remain, including the limited response of MSS CRC to immunotherapy, the high heterogeneity of CD4+ T cells, and the need to balance safety and efficacy in combination therapies. Future research should focus on precisely regulating CD4+ T cell differentiation, reversing immune resistance, optimizing engineered T cell design, and strengthening clinical translational studies, so as to achieve the transition from ″understanding the microenvironment″ to ″remodeling the microenvironment", ultimately providing more effective immunotherapy strategies for CRC patients.
Communication Author：MA Jian , Email:jma@hrbmu.edu.cn
SciCloud投稿系统