The roles of CD4+ T-Cells in tumor immunity

Abstract

Though the principal role of the immune system is to protect the host from invading pathogens, it also plays a major role in the elimination of tumors. T cells constitute the effector arm of the adaptive anti-tumor immunity. Increasing evidence indicates that among the subsets of T cells, CD4+ T cells are required for triggering both humoral and cell-mediated immune response and significantly contribute to tumor protection. The identification and characterization of CD4+ T cell lineage subsets began with a description of T-helper (Th)1 and Th2 cells and was subsequently extended to different other subgroups, such as Th17, Th9, Th22, and follicular helper T cells. In addition to these cells, some other cells with suppressive function had been identified, which are generally called regulatory T cells (Tregs). Each of the abovementioned subsets of CD4+ T cells plays different roles in establishing anti-tumor immunity. However, their exact roles in various types of solid tumors and hematological malignancies are not well-defined and remained controversial in some types of cancer. Considering the significant role of Th cells in triggering anti-tumor responses, these cells have become increasingly attractive options for immunological investigation and immunotherapy approaches for the treatment of cancer. Till date, various T-cells-based therapeutic strategies have been developed with the aim to achieving better immunity and then finding efficient therapeutic options to reduce cancer-related mortality. Here, after obtaining an overview of the CD4+ T cells subsets, differentiation, and functions, their roles in several types of cancer are reviewed. Subsequently, different therapeutic approaches that rely on T-cell-based immunotherapy, including adoptive cell transfer, targeting Tregs and other associated regulatory responses, and some suggested cytokine-based immunotherapies are discussed in detail.