MiR-195/-16 Family Enhances Radiotherapy via T Cell Activation in the Tumor Microenvironment by Blocking the PD-L1 Immune Checkpoint

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Zhen TaoKe Chen

Abstract

Radiotherapy is the standard treatment option for advanced prostate cancer. Unfortunately, despite significant advances in radiation delivery, prostate cancer radioresistance occurs in a large proportion of patients undergoing radiotherapy. As a way to enhance radiotherapy effectiveness, research advances into the mechanisms regulating the immune response have revived interest in combination radiation and immune-based therapies. miR-195/-16 family and PD-L1 levels were analyzed in samples from a GSE21032 data set. Kaplan-Meier analysis was used to evaluate the difference in biochemical recurrence-free survival associated with miR-195 and miR-16 expression. qRT-PCR and western blot were used to evaluate the miR-195, miR-16 and PD-L1 expression. Then, we used bioinformatics analysis and luciferase reporter assay to predict and confirm the miR-195 and miR-16 target gene. Finally, we elucidate the miR-195 and miR-16 function on immune evasion in the DU145/T cell co-culture model and syngeneic mouse model treated with radiotion through qRT-PCR, western blot, Flow cytometry and ELISA. High levels of miR-195 and miR-16 were positively correlated with the biochemical recurrence-free survival of prostate cancer patients. miR-195 and miR...Continue Reading

Citations

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