Immune evasion is an emerging hallmark of cancer progression. However, functional studies to understand the role of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are limited by the lack of available specific cell surface markers. We adapted a competitive peptide phage display platform to identify candidate peptides binding MDSCs specifically and generated peptide-Fc fusion proteins (peptibodies). In multiple tumor models, intravenous peptibody injection completely depleted blood, splenic and intratumoral MDSCs in tumor-bearing mice without affecting proinflammatory immune cell types, such as dendritic cells. Whereas control Gr-1–specific antibody primarily depleted granulocytic MDSCs, peptibodies depleted both granulocytic and monocytic MDSC subsets. Peptibody treatment was associated with inhibition of tumor growth in vivo, which was superior to that achieved with Gr-1–specific antibody. Immunoprecipitation of MDSC membrane proteins identified S100 family proteins as candidate targets. Our strategy may be useful to identify new diagnostic and therapeutic surface targets on rare cell subtypes, including human MDSCs.
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This work was supported by a Developmental Research Program award to H.Q. from the US National Cancer Institute Specialized Programs of Research Excellence in Lymphoma (P50 CA136411). We thank D. Hawke for performing proteomic sequencing and analyzing results, D. Kusewitt (M.D. Anderson Cancer Center) for providing S100A9-deficient mice and D. Gwak for editing assistance.
The authors declare no competing financial interests.
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Qin, H., Lerman, B., Sakamaki, I. et al. Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nat Med 20, 676–681 (2014). https://doi.org/10.1038/nm.3560
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