CD28 and neoplasm: Recent studies have demonstrated that a large fraction of tumor-resident CD8+ T cells have phenotypic changes associated with exhaustion and dysfunction typified by the loss of expression of the immune co-receptors CD27 and CD28, as well as the expression of immune checkpoint inhibitor proteins such as programed death receptor 1 (PD-1), T cell immunoglobulin and mucin protein 3 (Tim-3), among many others [3–5].