Abstract
Historically, CD8+ T cells have been considered the most relevant effector cells involved in the immune response against tumors and have therefore been the focus of most cancer immunotherapy approaches. However, CD4+ T cells and their secreted factors also play a crucial role in the tumor microenvironment and can orchestrate both pro- and antitumoral immune responses. Depending on the cytokine milieu to which they are exposed, CD4+ T cells can differentiate into several phenotypically different subsets with very divergent effects on tumor progression. In this review, we provide an overview of the current knowledge about the role of the different T helper subsets in the immune system, with special emphasis on their implication in antitumoral immune responses. Furthermore, we also summarize therapeutic applications of each subset and its associated cytokines in the adoptive cell therapy of cancer.
Keywords:
CD4+ T cell; adoptive cell therapy; cytokines; immunotherapy.
Grants and funding
S.K. is supported by the international doctoral program ‘i-Target: immunotargeting of cancer’ (funded by the Elite Network of Bavaria.), the Melanoma Research Alliance (grant number 409510), Marie Sklodowska-Curie Training Network for Optimizing Adoptive T Cell Therapy of Cancer (funded by the Horizon 2020 programme of the European Union; grant 955575), Else Kröner-Fresenius-Stiftung, German Cancer Aid, the Wilhelm-Sander-Stiftung, Ernst Jung Stiftung, Institutional Strategy LMUexcellent of LMU Munich (within the framework of the German Excellence Initiative), the Go-Bio-Initiative, the m4-Award of the Bavarian Ministry for Economical Affairs, Bundesministerium fur Bildung und Forschung, European Research Council (Starting Grant 756017 and PoC Grant 101100460.), Deutsche Forschungsgemeinschaft (DFG; KO5055-2-1 and 510821390), by the SFB-TRR 338/1 2021–452881907, Fritz-Bender Foundation, the bayerische Forschungsstiftung (BAYCELLATOR), Deutsche José Carreras Leukämie Stiftung and Hector Foundation.