This hypothesis has been suggested by Huang et al. who demonstrated that among patients treated with the anti-PD-1 agent pembrolizumab, the clinical benefit was strongly correlated with the magnitude of reinvigoration of exhausted CD8+ T cells (as indicated by Ki67 expression and IFN-γ production), but above all with the amount of initial tumor burden, with greater tumor burden resulting in lower response rates. The gene discussed is IFNG; the disease is neoplasm.