B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells

B7-H1 is an immunoglobulin-like immune suppressive molecule broadly detectable on the majority of human and rodent cancers, and its functions have been attributed to delivering an inhibitory signal to its counter-receptor programmed death-1 (PD-1) on T cells. Here we report that B7-H1 on cancer cell...

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Bibliographic Details
Published in:	Blood 2008-04, Vol.111 (7), p.3635-3643
Main Authors:	Azuma, Takeshi, Yao, Sheng, Zhu, Gefeng, Flies, Andrew S., Flies, Sarah J., Chen, Lieping
Format:	Article
Language:	eng
Subjects:	Animals Antigens, Surface - immunology Antineoplastic agents Apoptosis - drug effects Apoptosis - immunology Apoptosis Regulatory Proteins - immunology B7-1 Antigen - immunology B7-H1 Antigen Biological and medical sciences Cell Line, Tumor Enzyme Inhibitors - pharmacology fas Receptor - immunology Fundamental and applied biological sciences. Psychology Fundamental immunology General aspects Humans Immunity, Cellular - drug effects Immunity, Cellular - immunology Immunobiology Medical sciences Membrane Glycoproteins - immunology Mice Mice, Inbred DBA Modulation of the immune response (stimulation, suppression) Neoplasms - immunology Neoplasms - pathology Peptides - immunology Pharmacology. Drug treatments Programmed Cell Death 1 Receptor Signal Transduction - drug effects Signal Transduction - immunology Staurosporine - pharmacology T-Lymphocytes - immunology T-Lymphocytes - pathology
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Summary:	B7-H1 is an immunoglobulin-like immune suppressive molecule broadly detectable on the majority of human and rodent cancers, and its functions have been attributed to delivering an inhibitory signal to its counter-receptor programmed death-1 (PD-1) on T cells. Here we report that B7-H1 on cancer cells receives a signal from PD-1 to rapidly induce resistance against T cell–mediated killing because crippling signaling capacity of B7-H1 but not PD-1 ablates this resistance. Importantly, loss of B7-H1 signaling is accompanied by increased susceptibility to immune-mediated tumoricidal activity. In addition to resistance against T-cell destruction, B7-H1+ cancer cells also become refractory to apoptosis induced by Fas ligation or the protein kinase inhibitor Staurosporine. Our study reveals a new mechanism by which cancer cells use a receptor on immune cells as a ligand to induce resistance to therapy.
ISSN:	0006-4971 1528-0020