IFNG and neoplasm: Exhaustion occurs by a multifactorial etiology due to persistent tumor antigen exposure, loss of effector cytokine secretion/stimulation [Interleuken-2 (IL-2), Interferon (IFN)-gamma), immunosuppressive cell types (e.g. myeloid derived suppressor cells (MDSCs)], and immunophenotypic changes, including increased checkpoint inhibitor expression [programmed death receptor-1 (PD-1), cytotoxic T-lymphocyte antigen number 4 (CTLA-4), T-cell immunoglobulin mucin-3 (TIM-3), and Lymphocyte-activation gene 3 (LAG-3)] (23, 24).