CD4 and melanoma: Invasive melanoma is the most fatal type of skin cancer.1 Although treatment with immune checkpoint inhibitors improves clinical outcome for patients with melanoma, there is still a large portion of patients that do not respond to this line of therapy.2 3 Resistance to checkpoint blockade therapy has been associated with decreased numbers of tumor-infiltrating effector T cells and increased numbers of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory CD4+ T cells (CD4+ Tregs).