Abstract 7620: Immuno-transcriptomic profiling of blood and tumor tissue identifies gene signatures associated with immunotherapy response in metastatic bladder cancer

Abstract

Abstract Muscle-invasive bladder cancer (MIBC) accounts for 25% of bladder cancer cases. Despite the broader usage of immune checkpoint blockade targeting the PD-1/PD-L1 axis, the response rate and survival of patients remain low for this disease. Redirecting swiftly these patients toward alternative therapeutic strategies upon immunotherapy failure should be a priority. So far, no marker allows to precisely determine early outcome to the treatment.Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical response to immunotherapy. In this study, we used next generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed at identifying biomarkers associated with immunotherapy response and to assess the potential application of simple non-invasive blood biomarkers as therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICI. Interestingly, a common lymphocytic activation signature can be identified in both compartments associated with the efficient response to immunotherapy, including a blood specific CD8+ T cell activation/proliferation signature which predicts immunotherapy response. Citation Format: Pedro J. Romero, Emma Desponds, Davide Croci, Victoria Wosika, Noushin Hadadi, Sara Fonseca Cost, Laura Ciarloni, Marco Ongaro, Hana Zdimerova, Marine M. Leblond, Sahar Hosseinian-Ehrensberger, Grégory Verdeil. Immuno-transcriptomic profiling of blood and tumor tissue identifies gene signatures associated with immunotherapy response in metastatic bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7620.