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01.03.2020 | Original Article | Ausgabe 3/2020

Cancer Immunology, Immunotherapy 3/2020

Mass cytometry defines distinct immune profile in germinal center B-cell lymphomas

Zeitschrift:
Cancer Immunology, Immunotherapy > Ausgabe 3/2020
Autoren:
Mikael Roussel, Faustine Lhomme, Caroline E. Roe, Todd Bartkowiak, Pauline Gravelle, Camille Laurent, Thierry Fest, Jonathan M. Irish
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00262-019-02464-z) contains supplementary material, which is available to authorized users.
Parts of the results of this study were presented as poster in November 2018 at the 1st European Symposium on Myeloid Regulatory Cells in Health and Disease, in Essen (Germany).

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Abstract

Tumor-associated macrophage and T-cell subsets are implicated in the pathogenesis of diffuse large B-cell lymphoma, follicular lymphoma, and classical Hodgkin lymphoma. Macrophages provide essential mechanisms of tumor immune evasion through checkpoint ligand expression and secretion of suppressive cytokines. However, normal and tumor-associated macrophage phenotypes are less well characterized than those of tumor-infiltrating T-cell subsets, and it would be especially valuable to know whether the polarization state of macrophages differs across lymphoma tumor microenvironments. Here, an established mass cytometry panel designed to characterize myeloid-derived suppressor cells and known macrophage maturation and polarization states was applied to characterize B-lymphoma tumors and non-malignant human tissue. High-dimensional single-cell analyses were performed using dimensionality reduction and clustering tools. Phenotypically distinct intra-tumor macrophage subsets were identified based on abnormal marker expression profiles that were associated with lymphoma tumor types. While it had been proposed that measurement of CD163 and CD68 might be sufficient to reveal macrophage subsets in tumors, results here indicated that S100A9, CCR2, CD36, Slan, and CD32 should also be measured to effectively characterize lymphoma-specific tumor macrophages. Additionally, the presence of phenotypically distinct, abnormal macrophage populations was closely linked to the phenotype of intra-tumor T-cell populations, including PD-1 expressing T cells. These results further support the close links between macrophage polarization and T-cell functional state, as well as the rationale for targeting tumor-associated macrophages in cancer immunotherapies.

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