The multifaceted roles of CD4+ T cells and MHC class II in cancer surveillance

CD4 T cells exhibit diverse functions in cancer surveillance. Concordantly, single-cell transcriptional analyses have revealed several distinct CD4 T-cell differentiation states in tumours, including cytotoxic and regulatory subsets associated with favourable or unfavourable outcomes, respectively. These transcriptional states are determined and further shaped by dynamic interactions of CD4 T cells with different types of immune cells, stromal cells and cancer cells. Therefore, we discuss the cellular networks in the tumour microenvironment (TME) that either promote or impede CD4 T-cell cancer surveillance. We consider antigen/Major histocompatibility complexclass-II (MHC-II)-dependent interactions of CD4 T cells with both professional antigen-presenting cells and cancer cells, the latter of which can directly express MHC-II, at least in some tumours. Additionally, we examine recent single-cell RNA sequencing studies that have shed light on the phenotype and functions of cancer-specific CD4 T cells in human tumours.