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 ZhaoPublished 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.