CD4 and cancer: The prototypical immune checkpoint PD-1 is variably expressed at the transcript or protein level in human cytotoxic CD4+ T cells from cancer patients (Kitano et al., 2013; Oh et al., 2020; Cachot et al., 2021), and its surface expression decreases in longitudinal cytotoxic CD4+ T cell clones isolated from individual patients following ipilimumab treatment in concert with enhanced cytotoxic activity (Kitano et al., 2013).