Perforin and Granzyme B Expressed by Murine Myeloid-Derived Suppressor Cells: A Study on Their Role in Outgrowth of Cancer Cells

A wide-range of myeloid-derived suppressor cell (MDSC)-mediated immune suppressive functions has previously been described. Nevertheless, potential novel mechanisms by which MDSCs aid tumor progression are, in all likelihood, still unrecognized. Next to its well-known expression in natural killer ce...

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Bibliographic Details
Main Authors: Inès Dufait, Julian Pardo, David Escors, Yannick De Vlaeminck, Heng Jiang, Marleen Keyaerts, Mark De Ridder, Karine Breckpot
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/11/6/808
Description
Summary:A wide-range of myeloid-derived suppressor cell (MDSC)-mediated immune suppressive functions has previously been described. Nevertheless, potential novel mechanisms by which MDSCs aid tumor progression are, in all likelihood, still unrecognized. Next to its well-known expression in natural killer cells and cytotoxic T lymphocytes (CTLs), granzyme B (GzmB) expression has been found in different cell types. In an MDSC culture model, we demonstrated perforin and GzmB expression. Furthermore, similar observations were made in MDSCs isolated from tumor-bearing mice. Even in MDSCs from humans, GzmB expression was demonstrated. Of note, B16F10 melanoma cells co-cultured with perforin/GzmB knock out mice (KO) MDSCs displayed a remarkable decrease in invasive potential. B16F10 melanoma cells co-injected with KO MDSCs, displayed a significant slower growth curve compared to tumor cells co-injected with wild type (WT) MDSCs. In vivo absence of perforin/GzmB in MDSCs resulted in a higher number of CD8<sup>+</sup> T-cells. Despite this change in favor of CD8<sup>+</sup> T-cell infiltration, we observed low interferon-&#947; (IFN-&#947;) and high programmed death-ligand 1 (PD-L1) expression, suggesting that other immunosuppressive mechanisms render these CD8<sup>+</sup> T-cells dysfunctional. Taken together, our results suggest that GzmB expression in MDSCs is another means to promote tumor growth and warrants further investigation to unravel the exact underlying mechanism.
ISSN:2072-6694