Thus, to investigate whether PD-L1 expression could be restored, our preliminary study demonstrated that the commonly used therapeutics in RA, methotrexate and anti-TNF, modulate PD-L1 expression on isolated early RA synovial macrophages, suggesting that modulation of the PD-1 pathway may be a mechanism of action of these therapeutics in early disease [76]. This evidence concerns the gene TNF and rheumatoid arthritis.