207P Impact of lymphatic vessel derived oxysterol on anti-tumor immunity

Bioactive derivatives of cholesterol have been demonstrated to regulate immune cell function and migration, the tumor microenvironment (TME), consequently progression. Ch25h, a key enzyme involved in metabolism 25- hydroxycholesterol(25-HC) production, was positively correlated with overall survival melanoma, breast cancer colon patients. High Ch25h expression is good response immunotherapy melanoma glioblastoma Expression levels human tumors are also lymphatic signature. However, mechanism vessel expressed remain unknown. Mouse B16-OVA-VEGFC MC38 cancer, E0771 models used on conditional knockout mice C57/bl6 immunodeficient background study impact endothelial cells (LECs) derived oxysterol anti-tumor immunity. CpG-based vaccination activated CD8 T adoptive transfer LEC-derived under immunotherapy. Our RNA sequencing data lymphangiogenic murine showed an increase tumor-associated LECs. Using conditional-knockout mice, we found that deficiency LECs leads significant decrease interstitial 25HC, as well increased aggressiveness suppressed infiltration. Specific deletion impedes intra-tumoral effector accumulation upon transfer. Further, LEC-specific show earlier relapse experiments, whereas littermates maintain control growth. Mechanistically, anti-CSFR1 administration promotes groups, contrast, introducing 25-HC intratumorally can prevent LEC-Ch25h mice. results suggest novel active way vessels participating immunity by regulating through oxysterol.