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

Author:

Desponds Emma12,Croci Davide3,Wosika Victoria3,Hadadi Noushin3,Fonseca Costa Sara S.3,Ciarloni Laura3,Ongaro Marco12,Zdimerova Hana12,Leblond Marine M.12ORCID,Hosseinian Ehrensberger Sahar3,Romero Pedro3,Verdeil Grégory12ORCID

Affiliation:

1. Department of Oncology UNIL CHUV, University of Lausanne, 1015 Lausanne, Switzerland

2. Ludwig Institute for Cancer Research, University of Lausanne, 1015 Lausanne, Switzerland

3. Novigenix SA, 1066 Epalinges, Switzerland

Abstract

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.

Funder

INNOSUISSE

Swiss Cancer Research Foundation

Swiss National Science Foundation

Publisher

MDPI AG

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