Immuno-Transcriptomic Profiling of Blood and Tumor Tissue Identifies Gene Signatures Associated with Immunotherapy Response in Metastatic Bladder Cancer

• Published in: Cancers Vol. 16; no. 2; p. 433
• Main Authors: Desponds, Emma, Croci, Davide, Wosika, Victoria, Hadadi, Noushin, Fonseca Costa, Sara S., Ciarloni, Laura, Ongaro, Marco, Zdimerova, Hana, Leblond, Marine M., Hosseinian Ehrensberger, Sahar, Romero, Pedro, Verdeil, Grégory
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024
• Subjects: Analysis; Biomarkers; Bladder cancer; Blood; Cancer; Cancer immunotherapy; Cancer therapies; CD8 antigen; Cell activation; Cell death; Chemotherapy; Cloning; Decision making; Drug therapy; Ethylenediaminetetraacetic acid; Genes; Genetic aspects; Genomes; Immune checkpoint inhibitors; Immune system; Immunotherapy; Invasiveness; Lymphocytes T; Medical prognosis; Medical screening; Metastases; Metastasis; Next-generation sequencing; Patients; PD-1 protein; PD-L1 protein; RNA; RNA sequencing; T cells; Transcriptomics; Tumor microenvironment; Tumors; United States > US; Germany; bladder cancer; blood biomarkers; immunotherapy
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16020433

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 responses 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 to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a 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 ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response.