STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer.

Liya DingQiwei WangAntons MartincuksMichael J KearnsTao JiangZiying LinXin ChengChangli QianShaozhen XieHye-Jung KimInga-Maria LaunonenAnniina FärkkiläThomas M RobertsGordon J FreemanJoyce F LiuPanagiotis A KonstantinopoulosUrsula MatulonisHua YuJean J Zhao

Published in: Journal for immunotherapy of cancer (2023)

We elucidate an adaptive immunosuppression mechanism rendering resistance to PARPi in BRCA1-mutant ovarian tumors. This is mediated by enrichment of protumor TAMs propelled by PARPi-induced STAT3 activation in tumor cells. We also provide a new strategy to reshape the immunosuppressive TME with STING agonists and overcome PARPi resistance in ovarian cancer.

Keyphrases

cell proliferation
dna damage
dna repair
drug induced
innate immune