B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells
Takeshi Azuma, Sheng Yao, Gefeng Zhu, Andrew S Flies, Sarah J Flies, Lieping Chen, Takeshi Azuma, Sheng Yao, Gefeng Zhu, Andrew S Flies, Sarah J Flies, Lieping Chen
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 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.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2275025/bin/zh80070817560001.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2275025/bin/zh80070817560002.jpg)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2275025/bin/zh80070817560003.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2275025/bin/zh80070817560004.jpg)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2275025/bin/zh80070817560005.jpg)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2275025/bin/zh80070817560006.jpg)
Source: PubMed