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JCI Insight. 2017 Jan 12;2(1):e89140. doi: 10.1172/jci.insight.89140.

Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy.

Author information

1
Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology.
2
Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
3
Department of Dermatology, Gunma University Graduate School of Medicine, Gunma, Japan.
4
Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
5
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
6
Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan.
7
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, Sweden.
8
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
9
MediCity Research Laboratory, University of Turku, Turku, Finland.

Abstract

Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRPα signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8+ T cells. In addition, the anti-SIRPα Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRPα-nonexpressing tumor cells. Anti-SIRPα Abs thus warrant further study as a potential new therapy for a broad range of cancers.

PMID:
28097229
PMCID:
PMC5214103
DOI:
10.1172/jci.insight.89140
[Indexed for MEDLINE]
Free PMC Article

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