Abstract:
: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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Qin H,Lerman B,Sakamaki I,Wei G,Cha SC,Rao SS,Qian J,Hailemichael Y,Nurieva R,Dwyer KC,Roth J,Yi Q,Overwijk WW,Kwak LWdoi
10.1038/nm.3560subject
Has Abstractpub_date
2014-06-01 00:00:00pages
676-81issue
6eissn
1078-8956issn
1546-170Xpii
nm.3560journal_volume
20pub_type
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