title: Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts.
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.
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92627, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ngo
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92627, USA.
authors.forename: Arum
authors.initials: A
authors.lastname: Han
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92627, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Lakatos
authors.affiliation: Departments of Pediatrics and Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Debashis
authors.initials: D
authors.lastname: Sahoo
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92627, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Hachey
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Kipp
authors.initials: K
authors.lastname: Weiskopf
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: 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.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Boiko
mesh_terms: D000068816:Adapalene / Q000276:immunology* / Q000378:metabolism; D051928:CD47 Antigen / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009362:Neoplasm Metastasis; D010587:Phagocytosis / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051928:CD47 Antigen; C497894:CD47 protein, human; D000068816:Adapalene; D040281:Vascular Endothelial Growth Factor Receptor-1