Further showing a role for PD-1 outside of exhaustion, a study comparing CD4+ TILs in 34 patients with metastatic melanoma, grouped into young vs. old, showed that the younger patients had a greater percentage of memory T cells that expressed PD-1, Ki-67, and HLA-DR (another activation marker), compared with age matched controls; these memory and activation phenotypes were less distinct in older patients (148). The gene discussed is PDCD1; the disease is metastatic melanoma.