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• W4379980066 abstract "Introduction: Tumor-infiltrating regulatory T cells (Tregs) contribute to an immunosuppressive tumor microenvironment. Despite extensive studies, the prognostic impact of tumor infiltrating Tregs in non-Hodgkin lymphomas (NHL) remains unclear. Emerging studies suggest substantial heterogeneity in the phenotypes and suppressive capacity of Tregs, emphasizing the importance of understanding Treg diversity and the need for markers to identify highly suppressive Tregs. Methods: Live CD4+ T cells were obtained by FACS sorting from NHL malignant lymph nodes (diffuse large B cell lymphoma (DLBCL, n = 3), follicular lymphoma (FL, n = 3)), and healthy donor tonsils (n = 3) and subjected to single-cell RNA sequencing (scRNAseq), CITE-seq and scTCR-seq by the 10X Genomics platform. The computational framework of CIBERSORTx was used to generate a unique signature matrix for the Treg subsets identified by scRNAseq, to facilitate validation in separate scRNAseq cohorts (King, Sci Immunol 2021; Roider, Nat Cell Biol 2020; Steen, Cancer Cell 2021), and to impute frequencies of the Treg subsets and correlate with survival in cohorts with bulk RNAseq data (Steen, Haematologica 2019; Pastore, Lancet Oncol 2015). High-dimensional cytometry and functional immunosuppression assays were applied to characterize Treg subsets in single-cell suspensions from DLBCL, FLand healthy donors peripheral blood and tonsils. Spatial and neighborhood analysis were performed by Imaging Mass Cytometry on FL tissue. Results: We identified three distinct transcriptional states of Tregs; resting, activated and LAG3+FOXP3- Tregs. Activated Tregs were enriched in NHL tumors and had higher expression of checkpoint receptors (TNFRSF4, TNFRSF18, TIGIT), NF-κB pathway (NFKBIA, NFKBIZ, REL), chemokine receptors (CXCR4) and transcription factors (JUN, JUNB, BATF) compared to resting Tregs. Phenotypical characterization showed that activated Tregs co-expressed several checkpoint receptors (PD-1, TIGIT, CTLA4, ICOS, OX40) and had stronger immunosuppressive activity compared to resting Tregs. In FL tumor microenvironment, activated Tregs were found in closer proximity to CD4+ and CD8+ T cells than other cell types. Using a unique gene signature matrix for each Treg subset, we confirmed that activated Tregs were the major subset in FL, and high abundance was associated with adverse outcome in two independent FL cohorts. The research was funded by: The research was funded by: the foundation KG Jebsen, Centre for B-cell malignancies (Centre no.19 to E.B.S. and J.H.M), The Norwegian Cancer Society (162948 to K.H., and 182694 to E.B.S.), The Research Council of Norway (FRIMEDBIO 230817/F20, E.B.S.) and the American Association for Cancer Research (19-40-12-STEE to C.B.S). Keywords: aggressive B-cell non-Hodgkin lymphoma, indolent non-Hodgkin lymphoma, microenvironment No conflicts of interests pertinent to the abstract." @default.
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• W4379980066 date "2023-06-01" @default.
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• W4379980066 title "DIVERSITY OF INTRATUMORAL REGULATORY T CELLS IN B‐CELL NON‐HODGKIN LYMPHOMA" @default.
• W4379980066 doi "https://doi.org/10.1002/hon.3163_13" @default.
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