The role of CD4<sup>+</sup> T cells in tumor and chronic viral immune responses
Luoyingzi Xie, Jingyi Fang, Juncheng Yu, Weinan Zhang, Zhiqiang He, Lilin Ye, Huaizhi Wang
Abstract
Abstract Immunotherapies are mainly aimed to promote a CD8 + T cell response rather than a CD4 + T cell response as cytotoxic T lymphocytes (CTLs) can directly kill target cells. Recently, CD4 + T cells have received more attention due to their diverse roles in tumors and chronic viral infections. In antitumor and antichronic viral responses, CD4 + T cells relay help signals through dendritic cells to indirectly regulate CD8 + T cell response, interact with B cells or macrophages to indirectly modulate humoral immunity or macrophage polarization, and inhibit tumor blood vessel formation. Additionally, CD4 + T cells can also exhibit direct cytotoxicity toward target cells. However, regulatory T cells exhibit immunosuppression and CD4 + T cells become exhausted, which promote tumor progression and chronic viral persistence. Finally, we also outline immunotherapies based on CD4 + T cells, including adoptive cell transfer, vaccines, and immune checkpoint blockade. Overall, this review summarizes diverse roles of CD4 + T cells in the antitumor or protumor and chronic viral responses, and also highlights the immunotherapies based on CD4 + T cells, giving a better understanding of their roles in tumors and chronic viral infections.