The major findings are: 1) the expression of PDCD1, CD274 and PDCD1LG2 is elevated in synovial tissues at various stages of RA disease progression; 2) PD-1 is expressed on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells; 3) Nivolumab-responsive genes in TME are enriched in synovial biopsies; 4) serum sPD1 is elevated in ACPA+ early RA patients and, 5) PD-L1 protein is not available in the early RA synovium for agonistic interaction with PD-1. The gene discussed is CD4; the disease is rheumatoid arthritis.