Diversity of intratumoral regulatory T cells in B-cell non-Hodgkin lymphoma.

Autor:	Spasevska I; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Sharma A; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Steen CB; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway.; Division of Oncology, Stanford University School of Medicine, Stanford, CA., Josefsson SE; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway., Blaker YN; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway., Kolstad A; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Department of Oncology, Innlandet Hospital Trust, Lillehammer, Norway.; Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway., Rustad EH; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Meyer S; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Isaksen K; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Chellappa S; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Kushekhar K; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway., Beiske K; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Division of Cancer Medicine, Department of Pathology, Oslo University Hospital, Oslo, Norway., Førsund MS; Division of Cancer Medicine, Department of Pathology, Oslo University Hospital, Oslo, Norway., Spetalen S; Division of Cancer Medicine, Department of Pathology, Oslo University Hospital, Oslo, Norway., Holte H; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway., Østenstad B; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway., Brodtkorb M; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway., Kimby E; Department of Hematology, Karolinska Institute, Stockholm, Sweden., Olweus J; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Norway., Taskén K; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway., Newman AM; Division of Oncology, Stanford University School of Medicine, Stanford, CA.; Divisions of Hematology & Oncology, Department of Medicine, Stanford University, Stanford, CA., Lorenz S; Department of Core Facilities, Geonomics Core Facility, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Smeland EB; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Alizadeh AA; Division of Oncology, Stanford University School of Medicine, Stanford, CA.; Divisions of Hematology & Oncology, Department of Medicine, Stanford University, Stanford, CA., Huse K; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Myklebust JH; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B-cell malignancies, Institute of Clinical Medicine, University of Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Dec 12; Vol. 7 (23), pp. 7216-7230.
DOI:	10.1182/bloodadvances.2023010158
Abstrakt:	Tumor-infiltrating regulatory T cells (Tregs) contribute to an immunosuppressive tumor microenvironment. Despite extensive studies, the prognostic impact of tumor-infiltrating Tregs in B-cell non-Hodgkin lymphomas (B-NHLs) remains unclear. Emerging studies suggest substantial heterogeneity in the phenotypes and suppressive capacities of Tregs, emphasizing the importance of understanding Treg diversity and the need for additional markers to identify highly suppressive Tregs. Here, we applied single-cell RNA sequencing and T-cell receptor sequencing combined with high-dimensional cytometry to decipher the heterogeneity of intratumoral Tregs in diffuse large B-cell lymphoma and follicular lymphoma (FL), compared with that in nonmalignant tonsillar tissue. We identified 3 distinct transcriptional states of Tregs: resting, activated, and unconventional LAG3+FOXP3- Tregs. Activated Tregs were enriched in B-NHL tumors, coexpressed several checkpoint receptors, and had stronger immunosuppressive activity compared with resting Tregs. In FL, activated Tregs were found in closer proximity to CD4+ and CD8+ T cells than other cell types. Furthermore, we used a computational approach to develop unique gene signature matrices, which were used to enumerate each Treg subset in cohorts with bulk gene expression data. In 2 independent FL cohorts, activated Tregs was the major subset, and high abundance was associated with adverse outcome. This study demonstrates that Tregs infiltrating B-NHL tumors are transcriptionally and functionally diverse. Highly immunosuppressive activated Tregs were enriched in tumor tissue but absent in the peripheral blood. Our data suggest that a deeper understanding of Treg heterogeneity in B-NHL could open new paths for rational drug design, facilitating selective targeting to improve antitumor immunity. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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