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• W2893388531 abstract "ABSTRACT Anti-PD-1/anti-PD-L1 therapies have shown success in cancer treatment but responses are limited to ~ 15% of patients with lymphocyte infiltrated, PD-L1 positive tumors. Hence, strategies that increase PD-L1 expression and tumor infiltration should make more patients eligible for PD-1/PD-L1 blockade therapy, thus improving overall outcomes. PD-L1 expression on tumors is induced by IFNγ, a cytokine secreted by NK cells. Therefore, we tested if PM21-particle expanded NK cells (PM21-NK cells) induced expression of PD-L1 on tumors and if anti-PD-L1 treatment enhanced NK cell anti-tumor efficacy in an ovarian cancer model. Studies here showed that PM21-NK cells secrete high amounts of IFNγ and that adoptively transferred PM21-NK cells induce PD-L1 expression on SKOV-3 cells in vivo. The induction of PD-L1 expression on SKOV-3 cells coincided with the presence of regulatory T cells (Tregs) in the abdominal cavity and within tumors. In in vitro experiments, anti-PD-L1 treatment had no direct effect on cytotoxicity or cytokine secretion by predominantly PD-1 negative PM21-NK cells in response to PD-L1+ targets. However, significant improvement of NK cell anti-tumor efficacy was observed in vivo when combined with anti-PD-L1. PD-L1 blockade also resulted in increased in vivo NK cell persistence and retention of their cytotoxic phenotype. These results support the use of anti-PD-L1 in combination with NK cell therapy regardless of initial tumor PD-L1 status and indicate that NK cell therapy would likely augment the applicability of anti-PD-L1 treatment." @default.
• W2893388531 created "2018-10-05" @default.
• W2893388531 creator A5015610514 @default.
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• W2893388531 creator A5066032846 @default.
• W2893388531 date "2018-08-27" @default.
• W2893388531 modified "2023-10-11" @default.
• W2893388531 title "PD-L1 blockade enhances anti-tumor efficacy of NK cells" @default.
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• W2893388531 doi "https://doi.org/10.1080/2162402x.2018.1509819" @default.
• W2893388531 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6205063" @default.
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• W2893388531 hasPublicationYear "2018" @default.
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