Abstract 1174: Examining antitumorigenic effects of <i>Ruminococcus gnavus</i>

Abstract Melanoma is one of the most commonly occurring cancers in the world, with increasing occurrence over the past several decades. Common treatment regimens for melanoma include immune checkpoint inhibitor (ICI) therapy, which enhances interferon-γ production in CD8 T cells (Tc1). Despite showing efficacy in some patients, a majority of melanoma patients are resistant to ICI therapy. Prior studies have demonstrated the ability of the gut microbiota to impact Tc1 antitumor responses and ICI therapy efficacy. In analyzing top gut bacteria enriched in ICI-responders, Ruminococcus gnavus (R. gnavus) is a commonly identified species. Along with being ICI-responder associated, R. gnavus has been shown to catabolize dietary tryptophan into aryl hydrocarbon receptor (AHR) ligands.Here we demonstrate the tumor retraining properties of R. gnavus in subcutaneous, spontaneous, and metastatic cancer models. Further, gnotobiotic monocolonization experiments demonstrate the ability for this bacterium to restrain tumor growth independent of a complex microbiome. Analyzing the mechanism behind how R. gnavus causes melanoma growth suppression in our model, we have demonstrated requirements of bacterial viability and AHR activation. Colonization with R. gnavus at early, middle, and late-stage tumor timepoints was able to induce a significant Tc1 response locally in the tumor and systemically in tumor-draning lymph nodes and spleen. Finally, we found R. gnavus colonization to facilitate ICI efficacy in our model. This study uncovers a potential mechanism of how a common ICI-reponse associated bacterium enhances ICI efficacy in melanoma. Citation Format: Yue Zhang, Colin R. Laughlin, Amanda Lee, Catherine M. Phelps, Surya P. Pandey, Simran K. Randhawa, Alex C. McPherson, Jake H. Shapira, Reinhard Hinterleitner, Giorgio Trinchieri, Marlies Meisel. Examining antitumorigenic effects of Ruminococcus gnavus [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 1174.