CTLA4 and melanoma: Since melanoma is characterized as an “immune-cold” tumor with limited T cell infiltration and immunosuppressive TME,57 ICIs, including anti-PD-L1 antibody (αPD-L1) and anti-CTLA-4 antibody (αCTLA-4), display limited efficacy in increasing active effector T cells and inflammatory cytokines (Figures 5N–5R), resulting in only modest tumor cell death and growth inhibition at a dose of 30 μg per mouse (Figures 5S–5V).