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

• 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
• Subjects: MDSC; CD8+ T-cell; perforin; granzyme B; cancer
• Online Access: https://www.mdpi.com/2072-6694/11/6/808

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-γ (IFN-γ) 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.