Although our studies have shown that Tim-3−PD-1−CD8+ T cells produced more IFN-γ than Tim-3+PD-1+CD8+ T cells within TILs, the IFN-γ induction level is still lower than that produced by Tim-3−PD-1−CD8+ T cells in paraneoplastic tissues, supporting the hypothesis that the tumor microenvironment may up-regulation of inhibitory receptors. The gene discussed is HAVCR2; the disease is neoplasm.