000086997 001__ 86997
000086997 005__ 20200716101534.0
000086997 0247_ $$2doi$$a10.3390/cancers11060808
000086997 0248_ $$2sideral$$a115388
000086997 037__ $$aART-2019-115388
000086997 041__ $$aeng
000086997 100__ $$aDufait, Inès
000086997 245__ $$aPerforin and Granzyme B Expressed by Murine Myeloid-Derived Suppressor Cells: A Study on Their Role in Outgrowth of Cancer Cells
000086997 260__ $$c2019
000086997 5060_ $$aAccess copy available to the general public$$fUnrestricted
000086997 5203_ $$aA 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.
000086997 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B29$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2017-83120-C2-1-R
000086997 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000086997 590__ $$a6.126$$b2019
000086997 591__ $$aONCOLOGY$$b37 / 244 = 0.152$$c2019$$dQ1$$eT1
000086997 592__ $$a1.938$$b2019
000086997 593__ $$aOncology$$c2019$$dQ1
000086997 593__ $$aCancer Research$$c2019$$dQ1
000086997 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000086997 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, Julián$$uUniversidad de Zaragoza
000086997 700__ $$aEscors, David
000086997 700__ $$aDe Vlaeminck, Yannick
000086997 700__ $$aJiang, Heng
000086997 700__ $$aKeyaerts, Marleen
000086997 700__ $$aDe Ridder, Mark
000086997 700__ $$aBreckpot, Karine
000086997 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000086997 773__ $$g11, 6 (2019), 808 [17 pp.]$$pCancers$$tCancers$$x2072-6694
000086997 8564_ $$s1696035$$uhttps://zaguan.unizar.es/record/86997/files/texto_completo.pdf$$yVersión publicada
000086997 8564_ $$s103590$$uhttps://zaguan.unizar.es/record/86997/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000086997 909CO $$ooai:zaguan.unizar.es:86997$$particulos$$pdriver
000086997 951__ $$a2020-07-16-09:35:23
000086997 980__ $$aARTICLE