In HPD patients treated with ICIs, cytotoxic CD8+ T lymphocytes in the tumor microenvironment are depleted due to dysregulation, and hence the elevated expression of depletion signals such as TIGIT, CTLA-4, and TIM-3, leads to lower expression of cytokines such as IFN-γ and TNF-α, weakening anti-tumor immunity [23,24]. The gene discussed is CD8A; the disease is neoplasm.