Some T cell-derived biomarkers have also been found to be predictive of response to PD-1 blockade in patients with advanced melanoma; these biomarkers include high baseline CD8+ and PD-1+ density at the invasive tumor margin and inside the tumor, proximity between PD-1+ and PD-L1+ cells, clonal TCR repertoire (43, 242), BIM expression in tumor-reactive PD-1+CD8+ T cells (261, 262), and higher proportion of PD-1hiCTLA-4hi cells with a partially exhausted T cell phenotype (capable of producing IFN-γ but lost the ability to produce TNF-α and IL-2) within CD8+ TILs (263). The gene discussed is TNF; the disease is melanoma.