Abstract
Whereas immunotherapies have revolutionized the treatment of different solid and hematologic cancers, their efficacy in nodal peripheral T-cell lymphomas (PTCL) is limited, due to a lack of understanding of the immune response they trigger. To fully characterize the immune tumor microenvironment (TME) of PTCL, we performed spectral flow cytometry analyses on 11 angioimmunoblastic T-cell lymphomas (AITL), 7 PTCL, not otherwise specified (PTCL, NOS) lymph node samples, and 10 non-tumoral control samples. The PTCL TME contained a larger proportion of regulatory T cells and exhausted CD8+ T cells, with enriched expression of druggable immune checkpoints. Interestingly, CD39 expression was up-regulated at the surface of most immune cells, and a multi-immunofluorescence analysis on a retrospective cohort of 43 AITL patients demonstrated a significant association between high CD39 expression by T cells and poor patient prognosis. Together, our study unravels the complex TME of nodal PTCL, identifies targetable immune checkpoints, and highlights CD39 as a novel prognostic factor.
MeSH terms
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Aged
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Apyrase / genetics
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Apyrase / metabolism
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Biomarkers, Tumor
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Female
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Humans
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Immunophenotyping
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphoma, T-Cell / genetics
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Lymphoma, T-Cell / immunology
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Lymphoma, T-Cell / metabolism
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Lymphoma, T-Cell / pathology
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Lymphoma, T-Cell / therapy
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Lymphoma, T-Cell, Peripheral / genetics
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Lymphoma, T-Cell, Peripheral / immunology
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Lymphoma, T-Cell, Peripheral / pathology
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Lymphoma, T-Cell, Peripheral / therapy
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Male
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Middle Aged
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Prognosis
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Retrospective Studies
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Tumor Microenvironment* / immunology
Substances
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Apyrase
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Biomarkers, Tumor
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ENTPD1 protein, human
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Antigens, CD
Grants and funding
Funding: This project was funded by grants from la Ligue contre le Cancer, the ATIP-Avenir funds, and the Laboratory of Excellence (LabEx) Dev2Can (ANR-10-LABX-0061), to YGB. PS was supported by a scholarship from the Fondation pour la Recherche Médicale (FRM). AV was supported by a fellowship from the Association pour la Recherche contre le Cancer (ARC) Foundation.