CD4+ T cell help in cancer immunology and immunotherapy

Cancer immunotherapy aims to promote the activity of cytotoxic T lymphocytes (CTLs) within a tumour, assist the priming of tumour-specific CTLs in lymphoid organs and establish efficient and durable antitumour immunity. During priming, help signals are relayed from CD4(+) T cells to CD8(+) T cells by specific dendritic cells to optimize the magnitude and quality of the CTL response. In this Review, we highlight the cellular dynamics and membrane receptors that mediate CD4(+) T cell help and the molecular mechanisms of the enhanced antitumour activity of CTLs. We outline how deficient CD4(+) T cell help reduces the response of CTLs and how maximizing CD4(+) T cell help can improve outcomes in cancer immunotherapy strategies.