Article

Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis.

Center for Biomedical Research, University of Texas Health Center at Tyler, Tyler, TX 75708, USA.
Molecular Immunology (impact factor: 2.9). 04/2008; 45(5):1470-6. DOI:10.1016/j.molimm.2007.08.013 pp.1470-6
Source: PubMed

ABSTRACT Chemotherapy has been widely used in cancer treatment. However, the prognosis of the cancer patients following chemotherapy has not been substantially improved. Alternative strategies such as immunotherapy and their combinations with chemotherapy are now being considered. Yet, the effects of chemotherapy on the immune responses of cancer cells are not clear. Cancer immunoresistance and immune escape are major obstacles in immunotherapy. In the present studies, we examined the effects of chemopreventive agents, paclitaxel, etoposide and 5-fluorouracil, on the surface expression of programmed death-1-ligand 1 (PD-L1), a negative regulator of T cell anti-tumor immunity. Interaction of PD-L1 on cancer cells with programmed death receptor 1 (PD-1) on T cells has been reported to inhibit the proliferation of tumor-reactive cytotoxic T cells and induce T cell apoptosis, which could be an important mechanism in the development of cancer immunoresistance. We demonstrated that those chemopreventive agents were able to induce PD-L1 surface expression in human breast cancer cells, which then promoted PD-L1-mediated T cell apoptosis. Our studies reveal a potential link between chemotherapy and cancer immunoresistance.

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Keywords

cancer cells
 
Cancer immunoresistance
 
cancer patients
 
cancer treatment
 
chemopreventive agents
 
Chemotherapy
 
death receptor 1
 
death-1-ligand 1
 
etoposide
 
human breast cancer cells
 
immune responses
 
immunotherapy
 
induce PD-L1 surface expression
 
induce T cell apoptosis
 
negative regulator
 
potential link
 
present studies
 
T cell anti-tumor immunity
 
T cells
 
tumor-reactive cytotoxic T cells