1541 Stability of the gut microbiota during anti-pd1 immunotherapy defines complete response in melanoma patients

• DOI: 10.1136/jitc-2023-sitc2023.1541
• Publication Date: 2023-10-31T15:03:58Z
• Authors: Angeli DG Macandog; Carlotta Catozzi; Mariaelena Capone; Amir Nabinejad; Gabriele Madonna; Massimo Barberis; Pier Ferrucci; Nicola Segata; Luigi Buonaguro; Emilia Cocorocchio; Paolo A Ascierto; Teresa Manzo; Luigi Nezi
• Keywords: Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282

<h3>Background</h3> The advent of immune checkpoint inhibition (ICI) therapy markedly improved the outcome for melanoma. However, response remains heterogeneous, with about half patients being refractory or developing relapse. Although a causal link between gut microbiota and modulation antitumor has been established, current knowledge is limited to findings from cross-sectional analyses. Here, we follow melanoma over course anti-PD1 therapy, delineate changes related host identify factors involved. <h3>Methods</h3> To study response-related during ICI, unresectable two Italian hospitals (n=23) were followed at baseline immunotherapy (n=13 months) collect fecal blood samples along clinical information. Patients annotated by PFS RECIST 1.1. Additionally, tumor-free subjects used as reference compare diversity trends groups therapy. Finally, cross-study validation was carried on metagenomes (n=281) Europe (n=4), UK (n=2) USA (n=3) cohorts. <h3>Results</h3> Our results demonstrate that fairly variable ICI therapy; however, are less pronounced among complete responders (CR), especially later cycles. We validate longitudinally stable taxa in CR, which comprise mostly Clostridia taxa. These CR associate consistently positive systemic markers, supporting their immunomodulatory potential. At functional level, our data key role specific bacterial metabolic activities structural components driving productive response. will present also experimental validation. <h3>Conclusions</h3> Overall, propose stability consequential feature an immune-beneficial Clostridia-rich responders, exploits tumor antigen's cross presentation. <h3>Ethics Approval</h3> Collection included this approved local Ethical Committee European Institute Oncology (R845/18-IEO 889) Istituto Nazionale Tumori IRCCS Fondazione G. Pascale (37/22 oss).