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Tumor Cell PD-L1 May Regulate Chemotherapy-Induced Apoptosis in Colorectal Cancer

By: Cordi Craig
Posted: Friday, November 8, 2019

Increasing the expression of the immune checkpoint protein PD-L1 in patients with colorectal cancer may improve the effectiveness of chemotherapy, according to a study published in Oncogene. The study also found that the BRAF oncogene regulates the expression of PD-L1, and when mutated, it can increase PD-L1 expression in colorectal cancer cells.

“These findings, if verified by subsequent research, suggest that the level of tumor cell PD-L1 may be important in drug sensitivity and suggest that enhancing PD-L1 expression may be a potential strategy to improve treatment outcomes in this malignancy,” Frank A. Sinicrope, MD, of the Mayo Clinic, Rochester, Minnesota, stated in a press release.

Using the Cancer Genome Atlas Data Portal of the National Cancer Institute, the authors examined PD-L1 expression of human colorectal cancers and associated mutation data with patient survival. Increased tumor cell PD-L1 expression was associated with improved survival among patients expected to have received chemotherapy. In addition, removing the PD-L1 gene suppressed two proteins associated with chemotherapy-induced apoptosis. By contrast, restoring PD-L1 expression reversed this protein suppression. The results suggest PD-L1 shows potential as a predictive biomarker for how patients will respond to cancer treatment.

“Current therapies targeting PD-L1 are mainly focused on blocking or disrupting its function in tumor cells,” stated corresponding author Haidong Dong, MD, PhD, also of the Mayo Clinic. “[This work] is an idea-changing discovery that, if validated in clinical trials, would bring more benefit to patients with colon cancer that is resistant to current chemotherapy.”

Disclosure: The study authors reported no conflicts of interest.



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