Tumor-mediated bypass of immune checkpoint inhibitor (ICI) therapy with anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1, also called B7–H1 or CD274) or anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is a challenge of current years in the area of cancer immunotherapy. The gene discussed is CD274; the disease is cancer.