B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells

Takeshi Azuma, Sheng Yao, Gefeng Zhu, Andrew S. Flies, Sarah J. Flies, Lieping Chen

Research output: Contribution to journalArticlepeer-review

Abstract

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 resis-tance 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.

Original languageEnglish (US)
Pages (from-to)3635-3643
Number of pages9
JournalBlood
Volume111
Issue number7
DOIs
StatePublished - Apr 1 2008

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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