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20.08.2018 | Original Article

IL-10 inducible CD8⁺ regulatory T-cells are enriched in patients with multiple myeloma and impact the generation of antigen-specific T-cells

verfasst von: Julian Plaumann, Melanie Engelhardt, Mohamed H. S. Awwad, Hakim Echchannaoui, Eva Amman, Marc S. Raab, Jens Hillengass, Niels Halama, Brigitte Neuber, Carsten Müller-Tidow, Hartmut Goldschmidt, Michael Hundemer

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2018

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Abstract

Tumor-mediated immunosuppression via regulatory T-cells is a key player among the various immune-escape mechanisms in multiple myeloma. We analyzed the generation, distribution, function and immunophenotype of CD8⁺CD28⁻ regulatory T-cells in patients with multiple myeloma. Functionality of CD8⁺CD28⁻ T-cells was assessed by immunological assays using ex vivo generated antigen-specific T-cells from patients with plasma cell dyscrasias and healthy donors. Detailed analysis of distribution, immunophenotype and cytotoxic potential of CD8⁺CD28⁻ T-cells was performed by flow cytometry and ELISA. We found that the amount of CD8⁺CD28⁻ T-cells was directly correlated with the suppression of antigen-specific T-cell responses in patients with plasma cell dyscrasia. Analyzing the CD8⁺CD28⁻ T-cells in detail, increased numbers of these cells were observed in the bone marrow (i.e., tumor microenvironment) of patients with plasma cell dyscrasia. Furthermore, we identified the expression of lymphocyte function-associated antigen 1 (LFA-1) as a marker of immunosuppression and defined the CD8⁺CD28⁻CD57⁺LFA-1^high population as the relevant immunosuppressive compartment. These regulatory T-cells act as immunosuppressors via soluble factors and incubation with IL-10 augmented their immunosuppressive capacity. The immunosuppressive regulatory network of IL-10 and the CD8⁺CD28⁻CD57⁺LFA-1^high regulatory T-cells show unique characteristics and contribute to the tumor immune escape mechanism in patients with multiple myeloma.

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Titel: IL-10 inducible CD8+ regulatory T-cells are enriched in patients with multiple myeloma and impact the generation of antigen-specific T-cells
verfasst von: Julian Plaumann
Melanie Engelhardt
Mohamed H. S. Awwad
Hakim Echchannaoui
Eva Amman
Marc S. Raab
Jens Hillengass
Niels Halama
Brigitte Neuber
Carsten Müller-Tidow
Hartmut Goldschmidt
Michael Hundemer
Publikationsdatum: 20.08.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2018
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2230-0

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IL-10 inducible CD8⁺ regulatory T-cells are enriched in patients with multiple myeloma and impact the generation of antigen-specific T-cells

Abstract

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