Cruciferae-based oral selenium delivery system reprograms antitumor response and enhances the anti-tumor potency of natural killer cells

Abstract

Natural killer (NK) cell-based immunotherapy represents a promising approach for lung cancer treatment, but its clinical efficacy is limited by poor in vivo persistence and cytotoxicity. Selenium, an essential trace element with immunomodulatory and antitumor properties, offers therapeutic potential, but its application is constrained by low bioavailability. In this study, Chinese Kale (Brassica oleracea var. alboglabra, BOA) was used to construct an oral kale seedlings biotransformation nano-selenium delivery system (Se@BOA). By inducing mitochondrial apoptosis in tumor cells, Se@BOA could effectively reprogram non-small-cell lung cancer immune resistance and enhance the killing abilities of NK cells on A549 cells in vitro, and additionally promote the activation of innate immune cells as well as adoptive NK cells to lyse tumors in vivo. Further mechanistic studies demonstrated that Se@BOA sensitizes tumor cells to NK cells by triggering DNA damage and p53 signaling pathways to induce NKG2DLs and death receptor expression. Additionally, Se@BOA could activate the AHR-STAT3 signaling cascade and promote NKG2D and NKp44 receptor expression on NK cells and thus inhibit tumor immune escape. Taken together, these findings reveal a novel strategy to improve selenium bioavailability and enhance the antitumor efficacy of allogenic human NK cell infusions, potentially informing the development of a plant-derived oral selenium delivery system to support NK cell therapy against lung cancer.