Abstract P073: Gut microbiota shift in melanoma patients undergoing immunotherapy is associated with clinical response

Abstract

Abstract Background: The high resistance of melanoma to targeted therapy has made it a persistently lethal cancer type. Although the advent of immune checkpoint inhibition (ICI) therapy markedly improved outcome for melanoma in recent years, response remains heterogenous, with only 20-40% of patients achieving clinical response for anti-CTLA4 or anti-PD1 therapy. This variability in response has urged research towards host factors that drive response to immunotherapy, and studies have come out to show that the gut microbiota influences immunotherapy response. More importantly, mouse studies and more recent human clinical trials demonstrate that transplantation of responder (R) microbiota improves host immunity and alleviates tumor growth during immunotherapy. Although these findings confirm a close relationship between the gut microbiota and antitumor host immunity, FMT human clinical trials on melanoma patients report success in only 30-40% of patients, suggesting that current knowledge of underlying immunomodulatory mechanisms of the gut microbiota are still limited, and that analysis of data collected only before start of therapy is insufficient. Notably, there is a lack of published longitudinal studies that monitor gut microbiome changes during melanoma immunotherapy. Methods: We performed longitudinal analysis of the gut microbiota in melanoma patients undergoing NEOAJUVANT immunotherapy, revealing distinct dynamics between R and non-responders (NR) over the course of treatment. Sequencing data were paralleled with a quantitative analysis of circulating inflammatory molecules, suggesting a dynamic interaction between the gut microbiota and immune system. Here, we will present key modulators of the immune cell compartment. Conclusions: Overall, our results highlight the importance of longitudinal analysis to dissect the role of the gut microbiota on response to immunotherapy. Citation Format: Angeli Dominique Macandog, Carlotta Catozzi, Ester Cassano, Sara Gandini, Pier Francesco Ferrucci, Emilia Cocorocchio, Teresa Manzo, Luigi Nezi. Gut microbiota shift in melanoma patients undergoing immunotherapy is associated with clinical response [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P073.