Abstract 2260: Transcriptomic immuno-oncology investigation of B-cell lymphomas using a novel comparative workflow

Abstract

Abstract Patients with B-cell lymphoma currently have limited treatment options, often with serious side effects; for example, B-cell lymphoma patients undergoing chemo- and radiation therapies experience poor health from off-target toxicity. Similarly, though CD19 CAR T-cell therapy is very effective, patients suffer lifelong B-cell aplasia as a side effect. Comparing a cancer to an autoimmune disease in the same tissue type may grant us additional insights on the immune dysregulation of the cancer, leading to development of more immune-aware cancer treatments. We introduce a new data-driven comparative workflow for the analysis of immuno-oncology attributes by comparing a cancer and an autoimmune disease in the same tissue type. As an example use case, we compare primary B-cell lymphomas to primary B-cells from systemic lupus erythematosus with the goal of delineating new mechanisms that can be leveraged to treat B-cell lymphomas. Our analysis will utilize bulk RNA-sequencing (RNA-seq) of B-cells for initial discovery, followed by single-cell RNA-sequencing (scRNA-seq) of Peripheral Blood Mononuclear Cells (PBMCs) for validation. Our analytical framework incorporates differential gene analysis, GO Terms, known protein-protein interactions, principal component analysis, and machine learning for biomarker detection. Here, we describe our novel tool in detail and share the results of our lymphoma use case to gain a better understanding of the targetable immune-related attributes of B-cell lymphoma. We expect that this novel tool, along with the results of our B-cell lymphoma use case, will contribute to the continued development of immune-focused treatment options for B-cell lymphoma and other cancers. Citation Format: Naomi Rapier-Sharman, Michael T. Told, Sehi Kim, Kim L. O'Neill, Brett E. Pickett. Transcriptomic immuno-oncology investigation of B-cell lymphomas using a novel comparative workflow [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 2260.