86997 20200716101534.0 doi 10.3390/cancers11060808 sideral 115388 ART-2019-115388 eng Dufait, Inès Perforin and Granzyme B Expressed by Murine Myeloid-Derived Suppressor Cells: A Study on Their Role in Outgrowth of Cancer Cells 2019 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/DGA/B29 info:eu-repo/grantAgreement/ES/MINECO/SAF2017-83120-C2-1-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 6.126 2019 ONCOLOGY 37 / 244 = 0.152 2019 Q1 T1 1.938 2019 Oncology 2019 Q1 Cancer Research 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0003-0154-0730 Pardo, Julián Universidad de Zaragoza Escors, David De Vlaeminck, Yannick Jiang, Heng Keyaerts, Marleen De Ridder, Mark Breckpot, Karine 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 11, 6 (2019), 808 [17 pp.] Cancers Cancers 2072-6694 1696035 http://zaguan.unizar.es/record/86997/files/texto_completo.pdf Versión publicada 103590 http://zaguan.unizar.es/record/86997/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:86997 articulos driver 2020-07-16-09:35:23 ARTICLE