Immune exhaustion has been primarily centered on T cells, upregulating multiple checkpoint receptors including programmed cell death-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), lymphocyte-activation gene-3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), CD160, and CD244 (SLAMF4, 2B4) within the immunosuppressive tumor microenvironment (TME) [1–4]. The gene discussed is CD244; the disease is neoplasm.