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

Dufait, Inès ; Pardo, Julián (Universidad de Zaragoza) ; Escors, David ; De Vlaeminck, Yannick ; Jiang, Heng ; Keyaerts, Marleen ; De Ridder, Mark ; Breckpot, Karine

Resumen: 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-¿ (IFN-¿) 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.

Idioma: Inglés

DOI: 10.3390/cancers11060808

Año: 2019

Publicado en: Cancers 11, 6 (2019), 808 [17 pp.]
ISSN: 2072-6694

Factor impacto JCR: 6.126 (2019)

Categ. JCR: ONCOLOGY rank: 37 / 244 = 0.152 (2019) - Q1 - T1

Factor impacto SCIMAGO: 1.938 - Oncology (Q1) - Cancer Research (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B29
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2017-83120-C2-1-R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Inmunología (Dpto. Microb.Med.Pr.,Sal.Públ.)