Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects.
Haiyan BaiAlvaro S PadronYilun DengYiji J LiaoClare J MurrayCarlos OntiverosSuresh J KariAravind KancharlaAnand V R KornepatiMyrna GarciaRyan Michael ReyesHarshita B GuptaJose R Conejo-GarciaTyler J CurielPublished in: Journal for immunotherapy of cancer (2023)
Pharmacological tumor PDL1 depletion with chlorambucil targets tumor-intrinsic PDL1 signaling that mediates treatment resistance, especially in αPDL1-resistant tumors, generates PDL1-dependent tumor immunogenicity and inhibits tumor growth in immune-dependent and independent manners. It could improve treatment efficacy of selected agents in otherwise treatment-refractory, including αPDL1-refractory cancers, and is rapidly clinically translatable.