As far as immune checkpoint expression, the general consensus is that cytotoxic CD4+ T cells are lacking in expression of many conventional checkpoints at the level of transcript at least in human cancer (Zhang et al., 2018, 2019; Oh et al., 2020), although individual studies from human melanoma TIL point to some degree of expression of TNFRSF4 (OX40/CD134), TNFRSF9 (4-1BB/CD137), and TNFRSF18 (GITR) (Cachot et al., 2021, based on re-clustering of data from Sade-Feldman et al., 2018). This evidence concerns the gene TNFRSF4 and melanoma.