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Cell Rep. 2016 Aug 9;16(6):1701-1716. doi: 10.1016/j.celrep.2016.07.004. Epub 2016 Jul 28.

Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts.

Author information

1
Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92627, USA.
2
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92627, USA.
3
Departments of Pediatrics and Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
4
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
5
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
6
Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92627, USA. Electronic address: aboiko@uci.edu.

Abstract

The high rate of metastasis and recurrence among melanoma patients indicates the existence of cells within melanoma that have the ability to both initiate metastatic programs and bypass immune recognition. Here, we identify CD47 as a regulator of melanoma tumor metastasis and immune evasion. Protein and gene expression analysis of clinical melanoma samples reveals that CD47, an anti-phagocytic signal, correlates with melanoma metastasis. Antibody-mediated blockade of CD47 coupled with targeting of CD271(+) melanoma cells strongly inhibits tumor metastasis in patient-derived xenografts. This therapeutic effect is mediated by drastic changes in the tumor and metastatic site immune microenvironments, both of whichwhich exhibit greatly increased density of differentiated macrophages and significantly fewer inflammatory monocytes, pro-metastatic macrophages (CCR2(+)/VEGFR1(+)), and neutrophils, all of which are associated with disease progression. Thus, antibody therapy that activates the innate immune response in combination with selective targeting of CD271(+) melanoma cells represents a powerful therapeutic approach against metastatic melanoma.

PMID:
27477289
DOI:
10.1016/j.celrep.2016.07.004
[Indexed for MEDLINE]
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