CD4 and neoplasm: We find that in high TML SCCs, α-PD-1 therapy further elevates tumor cell pSmad3 signaling and increases the fraction of CD4+ T cells that are immunosuppressive Tregs (Foxp3 + CD25+), thus restraining the anti-tumor immune response to this checkpoint inhibitor, but a combination of α-TGFβ with α-PD-1 synergistically enhances anti-tumor responses.