CD4+ T Cells: Multitasking Cells in the Duty of Cancer Immunotherapy

Richardson, Jennifer R.; Schöllhorn, Anna; Gouttefangeas, Cécile; Schuhmacher, Juliane

SIMPLE SUMMARY: T cells bearing the co-receptor CD4 on their cell surface are a heterogeneous group of T lymphocytes that exert pro- or anti-inflammatory functions. Evidence from mouse models and cancer patients reveal that various CD4+ T cell subsets play an antagonistic role in the antitumor immune response. This review summarizes current knowledge on CD4+ T cell subsets, on how they impact tumor growth in patients, and which role these cells play in newest cancer immunotherapies. ABSTRACT: Cancer immunotherapy activates the immune system to specifically target malignant cells. Research has often focused on CD8+ cytotoxic T cells, as those have the capacity to eliminate tumor cells after specific recognition upon TCR-MHC class I interaction. However, CD4+ T cells have gained attention in the field, as they are not only essential to promote help to CD8+ T cells, but are also able to kill tumor cells directly (via MHC-class II dependent recognition) or indirectly (e.g., via the activation of other immune cells like macrophages). Therefore, immunotherapy approaches have shifted from only stimulating CD8+ T cells to targeting and assessing both, CD4+ and CD8+ T cell subsets. Here, we discuss the various subsets of CD4+ T cells, their plasticity and functionality, their relevance in the antitumor immune response in patients affected by cancer, and their ever-growing role in therapeutic approaches for human cancer.