期刊
CANCERS
卷 11, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/cancers11060808
关键词
MDSC; CD8+T-cell; perforin; granzyme B; cancer
类别
资金
- Scientific Fund Willy Gepts of the UZBrussel
- Strategic Research Program of the Vrije Universiteit Brussel
- Stichting tegen Kanker, Kom op tegen Kanker (Stand up to Cancer)
- Flemish cancer society
- Institute for Science and Innovation (IWT)
- Gobierno de Aragon/FEDER (B29), Ministerio de Economia y Competitividad [SAF2017-83120-C2-1-R]
- IWT
- Kom op tegen Kanker (Stand up to Cancer)
- Miguel Servet II Fellowship (Instituto de Salud Carlos III, Spain)
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(+) T-cells. Despite this change in favor of CD8(+) T-cell infiltration, we observed low interferon-gamma (IFN-gamma) and high programmed death-ligand 1 (PD-L1) expression, suggesting that other immunosuppressive mechanisms render these CD8(+) 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.
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