588 Caloric restriction sensitizes melanoma to anti-PD-1 immune checkpoint inhibition

Background Individual response to immune checkpoint inhibition (ICI) in patients with metastatic melanoma varies from 10–40% for monotherapy and 50–60% combination therapy [1]. Identification of adjuncts ICI further bridge treatment cure is imperative. We focus on caloric restriction (CR) as an adjunct anti-PD-1 given its inexpensive nature, relative ease application, increased tolerability compared fasting. Methods 12-week C57BL/6J mice were inoculated Yale University Mouse Melanoma (YUMM 1.7), randomized into diet groups αPD-1 control (IgG) day 12 (D12). Full ad lib fed while CR 40% calorically restricted based average daily food intake. Tumors measured every 3 days digital calipers (q3d). or was intraperitoneally injected starting D12 continuing q3d 7 injections. Mice sacrificed tumors harvested D31. RNA sequencing performed CD45+ CD3+ T cells. Results Under conditions, treated had significantly smaller tumor volumes the full cohort (D22, 271.15 m3 vs. 336.72 m3, p=0.031) persisted harvest (D31, 600.96 1039.84 p=0.034). A significant difference between cohorts observed at D28 (439.34 667.63 p=0.005) 884.08 p=0.009). However, no growth under conditions murine separately observed.On pathway enrichment analysis inflammatory response, cytokine-mediated, interferon-gamma, cell proliferation pathways downregulated + cohort. Notable genes found these include B-cell linker protein (BLNK), tyrosine-protein kinase Lyn (LYN), SYK (spleen tyrosine kinase), toll-like receptor (TLR) TLR4, TLR7, TLR8. Conclusions Caloric sensitizes YUMM 1.7 resulting decreased growth. show modulation a line, which has previously demonstrated limited αPD-1. In present study, may decrease inflammation via downregulation cytokine mediated pathways. Furthermore, reverse immunosuppressive microenvironment provide means increase therapy. References Ward WH, Farma JM. Cutaneous Melanoma: Etiology Therapy. Brisbane (AU): Codon Publications. 2017; Chapter 8. Ethics Approval This study approved by Committee Animal Resources (UCAR), UCAR-2018-014.