Our review covers the following steps of the “cancer-immunity” cycle as elegantly described by Chen and Mellman [11]: Step 1: release of cancer cell antigens through Immunogenic Cell Death (ICD); Step 2: cancer antigen presentation (release of cytokines, release of ATP, exposure of HMGB1/CRT, TLR engagement); Step 3: priming, activation or suppression T cells (CD28, CD137, CD27, CTLA-4 and PD-L1); and Steps 6–7: T cell recognition and tumor elimination major histocompatibility complex (MHC) and inhibitory ligand expression on tumors, leading to a potentiated or suppressed CTL response). The gene discussed is CD28; the disease is cancer.