Abstract
Abstract (a) Expansion of therapeutic strategies against diffuse large B-cell lymphoma (DLBCL) offers new opportunities to fight aggressive non-Hodgkin's lymphoma. Therapy approaches, such as R-CHOP and stem cell transplant, and CAR-T cell therapies are now available for the treatment of DLBCL. While the role of the tumor microenvironment (TME) during the therapeutic response is now recognized, the spatial organization and the communication between the diverse factors that compose the TME remains to be fully understood. In this study, we describe a new immunogram tool to help clinical researchers measure the tumor microenvironment contribution to drug efficacy or toxicity in DLBCL context. (b) In a previous work, using a high-quality testing and innovative multimodal and integrative approach, we constructed the first Veracyte Biopharma Atlas for DLBCL lesions. Based on this knowledge and the understanding of the immune contexture of tumors, we constructed an immunogram using the scoring of clinically relevant biomarkers. Our immunogram scoring approach is composed of key features driving computational derivation of DLBCL Atlas clusters, which include immune gene signatures, immune cell phenotyping combined with spatial information, and genomic and clinical parameters. (c) Patterns that strongly associated with CAR-T treatment response were determined. In addition, promising results have been obtained in the prediction to CAR-T toxicity related to T-regulatory cells or R-CHOP response with transcriptomic signature. (d) Retrospective analysis of CAR-T clinical trial data and tumor biopsies highlighted the Veracyte Immunogram as a powerful tool to score the patient probability of response to CAR-T. This work provides the framework for identification of predictors of response to therapy, potential targets of interest or biomarkers that could be applied in future clinical trials. Citation Format: Michael D. Mattie, Regis Perbost, Sarah Turcan, Corinne Danan, Frederick L. Locke, Sattva S. Neelapu, David B. Miklos, Caron A. Jacobson, Lazaros J. Lekakis, Yi Lin, Armin Ghobadi, Jenny J. Kim, Zixing Wang, Allen Xue, Simone Filosto, Nathalie Scholler, Jerome Galon. Defining the cancer Immunogram using multimodal analysis to guide immunotherapy in diffuse large B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5879.
