P1206: A SINGLE-CELL MULTI-OMIC AND SPATIAL ATLAS OF NODAL B CELL NON-HODGKIN LYMPHOMAS REVEALS PLASTICITY IN B CELL MATURATION AS A DRIVER OF INTRATUMOR HETEROGENEITY

• DOI: 10.1097/01.hs9.0000971720.86618.0c
• Publication Date: 2023-08-08T16:09:07Z
• Authors: Donnacha Fitzgerald; Artur Kibler; Marc-A. Baertsch; Tobias Roider; Harald Vohringer; Anastasiia Horlova; Anna Mathioudaki; Bettina Budeus; Mareike Knoll; Erin Chung; Johannes Mammen; Leandra Caille; Verena Passerini; Felix Czernilofsky; Linsha LI; Oliver Weigert; Judith B. Zaugg; Gary P. Nolan; Marc Seifert; Wolfgang Huber; Sacha Dietrich
• Keywords: Follicular lymphoma

Topic: 20. Lymphoma Biology & Translational Research Background: Intratumor heterogeneity (ITH) is increasingly recognized as an essential factor in the variability of B cell non-Hodgkin lymphoma (B-NHL) patient outcomes. It well established that distinct nodal (NBNHL) entities originate from different stages humoral affinity maturation process, but drivers ITH are not understood. Aims: In this study, we aimed to characterize B-NHL and investigate its relationship with process. Methods: 51 diffuse large (DLBCL), follicular (FL), mantle (MCL), marginal zone (MZL), non-malignant reactive lymph node (rLN) samples patients were sequenced CITE-Seq (coupling single-cell RNA-seq surface epitope profiling). Transcription activities copy number variants (validated against targeted DNA sequencing) inferred computationally gene expression, while receptor clones determined VDJ profiling. Spatial relationships highly multiplexed immunochemistry (CODEX). Informed by expression signatures RNA sequencing FACS-identified states, a reference map was constructed nodes. This used classify states malignant logistic regression, which verified refined their marker profiles. Using shared features between CODEX panels, similarly classified spatial data microenvironments characterized cellular neighborhood analysis. (Fig A) Results: As context, also observed among cells most NBNHL tumors. BCR-sequencing light chain restriction confirmed intra-tumor monoclonal, therefore arose same origin. Although commonalities composition existed within entities, such abundance germinal center (GC) DLBCL memory MZL, high state proportions samples. For example, ABC FL tumors frequently contained both GC post-GC subpopulations. mediators process remained active malignancy. Copy variation tumor, indicating genetic can arise at sequential existent typically occupied niches. architecture disruption microenvironmental across tumors, tumor often maintained proximity dendritic helper T cells, key Summary/Conclusion: Our findings reveal halted during malignancy, remains continuous divergent central inter- intratumor variation. be subject occupy niches retaining interactions signals enable B)Keywords: development, lymphoma, subsets, OMICS