Optimization of PD-1 / PD-L1 Blockade to Increase NK Cells Cytotoxicity in Killing Cancer Cells: Article Review

Abstract

Anti-PD-1 and anti-PD-L1 are therapies that have shown success in cancer treatment. However, while treating cancer with PD-1/PD-L1 blockade is similar, the clinical response rate is still low in certain cancers at around 40%. Therefore, therapeutic strategies are needed to increase PD-L1 expression and optimize PD-1/PD-L1 blockade therapy, so as to improve satisfactory therapeutic results. In tumors, IFNγ induces the expression of PD-L1 which is a cytokine secreted by Natural Killer cells. A study showed that PM21-NK cells induced large amounts of IFNγ and transfected PM21-NK cells adaptively induced PD-L1 expression. In in vitro experiments, anti-PD-L1 treatment had no direct effect on cytotoxicity or cytokine secretion by PD-1 negative PM21-NK cells in response to PD-L1+ targets. However, in vivo a significant increase in the antitumor effect of Natural Killer cells was found when combined with anti-PD-L1. PD-L1 blockade also resulted in increased persistence of Natural Killer cells in vivo and retention of their cytotoxic phenotype. These results support the use of anti-PD-L1 in combination with Natural Killer cell therapy regardless of baseline tumor PD-L1 status and suggest that Natural Killer cell therapy will likely increase the applicability of anti-PD-L1 treatment. In this review article, the author will discuss the method of optimizing PD-L1 blockade combined with Natural Killer cell therapy to increase the efficacy of treatment on cancer stem cells in the dormant phase.