Tumor-Infiltrating Monocytic Myeloid-Derived Suppressor Cells Mediate CCR5-Dependent Recruitment of Regulatory T Cells Favoring Tumor Growth

作者: Eva Schlecker , Ana Stojanovic , Christian Eisen , Christian Quack , Christine S. Falk

DOI: 10.4049/JIMMUNOL.1201018

关键词:

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

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