Deciphering CD4⁺ T cell-mediated responses against cancer

It's been long thought that CD8⁺ cytotoxic T cells play a major role in T cell-mediated antitumor responses, whereas CD4⁺ T cells merely provide some assistance to CD8⁺ T cells as the "helpers." In recent years, numerous studies support the notion that CD4⁺ T cells play an indispensable role in antitumor responses. Here, we summarize and discuss the current knowledge regarding the roles of CD4⁺ T cells in antitumor responses and immunotherapy, with a focus on the molecular and cellular mechanisms behind these observations. These new insights on CD4⁺ T cells may pave the way to further optimize cancer immunotherapy.