Tumour necrosis factor-alpha (TNF-α) and Interferon-gamma (IFN-γ) released by CD4+ Th1 T cells and CD8+ cytotoxic T cells trigger senescence and cell death in tumour cells and efficacy of ICI is dependent on tumour cell responsiveness to IFN-γ as evidenced by the emergence of adaptive resistance to ICI in some patients mediated through accumulated mutations in genes coding for JAK-STAT signalling and antigen processing and presentation [102,103,104,105]. The gene discussed is CD8A; the disease is neoplasm.