癌症免疫疗法的进步改变了癌症治疗，并在许多患者中实现了前所未有的反应。不断增长的新型疗法——包括免疫检查点抑制 (ICI)、过继性 T 细胞疗法 (ACT) 和癌症疫苗——反映了癌症免疫疗法的成功。这些治疗方式的治疗益处通常归因于抗肿瘤 CD8 T 细胞反应的数量和质量的增强。尽管如此，CD4 T 细胞现在被认为在抗肿瘤免疫反应的启动阶段和效应阶段发挥着关键作用。除了通过共刺激和细胞因子产生来提供 T 细胞帮助外，CD4 T 细胞还可以直接对表达 MHC II 类的肿瘤细胞或肿瘤微环境 (TME) 内的其他细胞具有细胞毒性。 TME 内特定 CD4 T 细胞群的存在及其内在可塑性可以代表对免疫检查点抑制剂、疫苗和嵌合抗原受体 (CAR) T 细胞疗法的临床反应的重要决定因素。了解特定 CD4 T 细胞类型的抗肿瘤功能是如何被诱导的，同时限制其促肿瘤属性，将使免疫疗法更加成功。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Advances in cancer immunotherapy have transformed cancer care and realized unprecedented responses in many patients. The growing arsenal of novel therapeutics - including immune checkpoint inhibition (ICI), adoptive T cell therapies (ACTs), and cancer vaccines - reflects the success of cancer immunotherapy. The therapeutic benefits of these treatment modalities are generally attributed to the enhanced quantity and quality of antitumor CD8+ T cell responses. Nevertheless, CD4+ T cells are now recognized to play key roles in both the priming and effector phases of the antitumor immune response. In addition to providing T cell help through co-stimulation and cytokine production, CD4+ T cells can also possess cytotoxicity either directly on MHC class II-expressing tumor cells or to other cells within the tumor microenvironment (TME). The presence of specific populations of CD4+ T cells, and their intrinsic plasticity, within the TME can represent an important determinant of clinical response to immune checkpoint inhibitors, vaccines, and chimeric antigen receptor (CAR) T cell therapies. Understanding how the antitumor functions of specific CD4+ T cell types are induced while limiting their protumorigenic attributes will enable more successful immunotherapies.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.