The epigenetically regulated aberrant expression of immune checkpoints (ICs), including PD-1, CTLA-4, TIM-3 (T-cell immunoglobulin and mucin-domain containing-3), LAG-3 (lymphocyte-activation gene 3), TIGIT (T-cell immunoreceptor with Ig and ITIM domains), VISTA (V-domain Ig suppressor of T-cell activation), CD276 (B7-H3), B7-H4 (VTCN1/B7x/B7S1/B7 homolog 40), IDO-1 (indoleamine 2,3-dioxygenase 1), CD161, CD38, CD93, and CD47 may result in the induction of an immune-suppressive environment, which helps tumor cells to evade immune destruction [12,59,60]. The gene discussed is VTCN1; the disease is neoplasm.