Researchers from The University of Texas MD Anderson Cancer Center have uncovered the mechanism by which the tumor suppressor gene p53 regulates the molecule programmed cell death protein 1 (PD-L1) in small cell lung cancer. The study entitled “p53 regulation of PDL1 is mediated through miR-34a” was presented during the 2015 American Association for Cancer Research (AACR) Annual Meeting in Philadelphia, PA.
Clinical studies have tested promising therapies for several types of cancer, including non-small cell lung cancer (NSCLC), by targeting PD1/PDL1 signaling, a pathway that contributes to the immune evasion of cancer. However, the regulation of PDL1 expression is not well understood. Notably, the treatment inhibiting the PD-L1 protein does not function for all patients.
The authors had previously found that the microRNAs 200 (miR-200s) family directly regulates PDL1. The miR-200s family has been found to be deregulated in several types of cancers, where they have a crucial role in tumor initiation, maintenance, malignant metastasis and chemotherapy resistance.
James Welsh, M.D., senior author of the study, said in a news release that the team identified a new mechanism by which p53 regulates PD-L1 and tumor immune evasion through the regulation of miR-34a expression.
The mutated tumor suppressor gene p53 is involved in the growth of several tumors and miR-34a is a gene frequently observed in the lung but in situations of cancer, it is normally absent or expressed at low levels. “Although clinical studies have shown promise for targeting PD-1/PD-L1 signaling in non-small cell lung cancer, little is known about how PD-L1 expression is regulated,” said Dr. Welsh, who added that PD-L1 expression is regulated by miR-34a which in turn is activated by p53.
“Our results suggest that miR-34a delivery combined with standard therapies, such as radiotherapy, may represent a novel therapeutic approach for lung cancer,” said Dr. Angelica Cortez, first author of the study.
A better understanding of the regulation mechanism of the PD1/PDL1 signaling pathway will contribute to the development of novel treatments for cancer patients. Overall, this study suggested that delivery of miR-34a to cancer cells in combination with standard therapies, such as radiotherapy, may be a new potential therapeutic strategy for lung cancer.