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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3635-3643.
Prepublished online as a Blood First Edition Paper on January 25, 2008; DOI 10.1182/blood-2007-11-123141.
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Submitted November 15, 2007
Accepted January 12, 2008
B7-H1 is a ubiquitous anti-apoptotic receptor on cancer cells
Takeshi Azuma, Sheng Yao, Gefeng Zhu, Andrew S. Flies, Sarah J. Flies, and Lieping Chen*
Department of Dermatology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
* Corresponding author; email: lchen42{at}jhmi.edu.
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 of cancer cells utilize receptors on immune cells as ligands to induce resistance to therapy.
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