Examining methotrexate’s safety and efficacy in combination with immune checkpoint inhibitors to control immune related inflammatory arthritis in cancer

Abstract Immune checkpoint inhibitors (ICIs) are associated with high rates of toxic side effects known as immune related adverse events such inflammatory arthritis (ir-RA). ir-RA is empirically treated drugs for rheumatoid methotrexate (MTX) and hydroxychloroquine which was recently shown to reduce the anti-tumor benefit ICIs in mouse models cancer. We have set out determine safety MTX use combination ICIs, its effect on anti-tumoral response efficacy treating a novel arthritis-B16 PD-L1 tumor model. observed that did not diminish our melanoma model significantly altered intra-tumoral CD8 +T cell population by promoting formation central memory cells diminishing PD1 expression. identified acts neuropilin-1 (NRP1), receptor exhaustion marker terminal limiting tumors. treatment vitro reduces expression NRP1 stimulated cells. also advanced development arthritis-tumor showing can control inflammation delayed type hypersensitivity (DTHA) reduced frequency Th1 Th17 popliteal lymph nodes mice, crucial role ir-RA. Together these results show safe effective DTHA mimics profile With combined we will be able assess MTX’s controlling bearing mice.