Role and Potential of Different T Helper Cell Subsets in Adoptive Cell Therapy

Simple Summary While most cancer immunotherapies have focused on CD8(+) T cells as the main drivers of antitumor immunity, increasing evidence indicates that CD4(+) T cells also play a central role in the elimination of tumors. Naive CD4 T cells can be polarized towards different helper subsets, which can drastically affect the antitumor response through interactions with other cell types and the tumor microenvironment. In this review, we provide an overview of the role of different T helper subsets in the immune system, their implications in cancer immunology, and their applications in adoptive T-cell therapy. 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.