Abstract 5872: The gut microbiota from vasoactive intestinal peptide knock-out mice confers resistance to the growth of leukemia in wild-yype mice

Mice Resistance to Leukemia via Gut Microbiota Transfer Vasoactive Intestinal Peptide (VIP) regulates adaptive immunity through receptors expressed in T lymphocytes, VPAC1andVPAC2. VIP over production in leukemia suppresses immune function, facilitating cancer progression. VIP-knockout (VIP-KO) mice show a survival advantage against leukemia, likely due to gut microbiota-mediated immune response regulation. Cohousing enables gut microbiota transfer from VIP-KO to wild-type (WT) mice via coprophagy, potentially enhancing WT mice's resistance to leukemia. This study investigates whether cohousing WT and VIP-KO mice alters WT gut microbiota and confers resistance to leukemia challenge. Eighty mice, 42VIP-KO 38WT, were cohoused across 10cages for six weeks. Blood and stool samples were collected pre- and post-cohousing for immune and microbiome analyses. Mice were injected with syngeneic CD1498leukemiacells post-cohousing and monitored for survival. Gender differences in survival outcomes were also assessed. WT mice cohoused with VIP-KO mice demonstrated significant colonization by VIP-KO-derived gut microbiota, including Ruminococcus gnavus and Lactobacillus murinus, characterized by lower gut pH. Cohousing improved WT survival rates after leukemia challenge(p<0.009), producing long-term survivors. VIP-KO mice showed the highest presence of R. gnavus after cohousing (p=0.017)Cohousing-induced microbiota transfer enhances leukemia resistance in WT mice through gut microbiota-mediated immune modulation. Survival improvements are independent of gender, underscoring the robustness of this therapeutic strategy. These findings highlight microbiota-targeted therapies, such as fecal microbiota transplantation, as promising approaches for leukemia treatment. Future studies will evaluate combined microbiota transfer and VIP antagonism therapies i.e. ANT308tooptimizeoutcomes. Wild Type cohousing had a significance of p<0.001. Knockout cohousing had a significance of p<0.009. Wild type mice had the highest median survival time at 27days. Citation Format: Kayla Robinson, Shayna Jankowski, Jian Ming Li. The gut microbiota from vasoactive intestinal peptide knock-out mice confers resistance to the growth of leukemia in wild-yype mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5872.