Harnessing Antitumor CD4(+) T Cells for Cancer Immunotherapy

SIMPLE SUMMARY: Diverse evidence revealed that CD4(+) T cells play an important role in antitumor immunity by promoting or suppressing cytotoxic T cell responses. This review outlines the role of CD4(+) T subsets within the tumor microenvironment and summarizes the latest progress regarding their potentials in cancer immunotherapy and methods for improving outcomes in cancer strategies by modulating CD4(+) T responses. ABSTRACT: Over the past decades, CD4(+) T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4(+) T cells during antitumor immunity. CD4(+) T cells can either suppress or promote the antitumor cytotoxic CD8(+) T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different CD4(+) T cell subsets in cancer immune response and their contribution during cancer therapies. Specifically, we focus on the latest progress regarding the impact of CD4(+) T cell modulation on immunotherapies and other cancer therapies and discuss the prospect for harnessing CD4(+) T cells to control tumor progression and prevent recurrence in patients.