The outstanding antitumor capacity of CD4⁺ T helper lymphocytes

Over the past decades, tumor-resident immune cells have been extensively studied to dissect their biological functions and clinical roles. Tumor-infiltrating CD8⁺ T cells, because of their cytotoxic and killing ability, have been under the spotlight for a long time, whereas CD4⁺ T cells are considered just a supporting actor in the field of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the ability of CD4⁺ T cells in eradicating solid tumors, and their functions in mediating antitumor immunity have been investigated in various orientations. In this review, we highlight the pivotal role of CD4⁺ T cells in eliciting vigorous antitumor immune responses, summarize key signaling axes and molecular networks behind these antitumor functions, and also propose possible targets and promising strategies which might translate into more efficient immunotherapies against human cancers.