CTLA4, PD1 and ICOS are now recognized targets in cancer immunotherapy, leading to an interest in novel Ig SF co-inhibitory receptors such as Lymphocyte activation gene-3 (Lag-3), T-cell (or transmembrane) immunoglobulin and mucin domain 3 (Tim-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), to address CTLA-4 and PD-1 checkpoint inhibitor non-responders. The gene discussed is HAVCR2; the disease is cancer.