Chronic high-dose IFN-γ release [422], loss of the IFN-γ receptor [423], prolonged IFN-γ signaling in tumor cells, and PD-L1 expression (cancer and immune infiltrating cells) [424,425], may induce apoptosis in CD4+ T-cells, suppress immune and secondary antitumor immune response [176], cause immune evasion adaptive immune resistance to immune checkpoint therapy [177]. Here, CD4 is linked to neoplasm.