Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth

• Verfasst von: Schlecker, Eva [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth
• Verf.angabe: Eva Schlecker, Ana Stojanovic, Christian Eisen, Christian Quack, Christine S. Falk, Viktor Umansky, and Adelheid Cerwenka
• Jahr: 2012
• Umfang: 10 S.
• Fussnoten: Gesehen am 09.05.2018
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Rockville, Md. : American Association of Immunologists, 1916
• Jahr Quelle: 2012
• Band/Heft Quelle: 189(2012), 12, Seite 5602-5611
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.1201018
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1574284169

Abstract

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells in cancer patients and tumor-bearing mice that potently inhibits T cell responses. During tumor progression, MDSCs accumulate in several organs, including the tumor tissue. So far, tumor-infiltrating MDSC subpopulations remain poorly explored. In this study, we performed global gene expression profiling of mouse tumor-infiltrating granulocytic and monocytic (MO-MDSC) subsets compared with MDSCs from peripheral blood. RMA-S lymphoma-infiltrating MO-MDSCs not only produced high levels of NO and arginase-1, but also greatly increased levels of chemokines comprising the CCR5 ligands CCL3, CCL4, and CCL5. MO-MDSCs isolated from B16 melanoma and from skin tumor-bearing ret transgenic mice also expressed high levels of CCL3, CCL4, and CCL5. Expression of CCR5 was preferentially detected on regulatory T cells (Tregs). Accordingly, tumor-infiltrating MO-MDSCs directly attracted high numbers of Tregs via CCR5 in vitro. Intratumoral injection of CCL4 or CCL5 increased tumor-infiltrating Tregs, and deficiency of CCR5 led to their profound decrease. Moreover, in CCR5-deficient mice, RMA-S and B16 tumor growth was delayed emphasizing the importance of CCR5 in the control of antitumor immune responses. Overall, our data demonstrate that chemokines secreted by tumor-infiltrating MO-MDSCs recruit high numbers of Tregs revealing a novel suppressive role of MDSCs with potential clinical implications for the development of cancer immunotherapies.