Elevated levels of immune checkpoint proteins such as PD–L1, PD–L2, LAG–3, and TIM–3, alongside the co-stimulatory molecule CD28, point towards a state of dysregulated T-cell and immune activation and exhaustion, potentially contributing to a dysfunctional, exhausted, and inflammatory immune phenotype that compromises the host’s ability for an effective anti-tumor response (10, 20, 21). The gene discussed is CD28; the disease is neoplasm.