CD4 and melanoma: Another important evidence about the possible involvement of non-Tregs CD4+ lymphocytes in determining HPD comes from the work by Zappasodi et al. The Authors observed, in a mouse model of melanoma, that a subpopulation of CD4+Foxp3−PD-1high, named 4PD-1hi, is present in the TME and that its frequency is correlated with the tumor size.