Translational selenium nanoparticles enhance NKG2D-mediated cytotoxicity of NK cells against malignant pleural mesothelioma cells through the TrxR1-pSTAT3 pathway

Abstract

Malignant pleural mesothelioma (MPM) constitutes a rare classification of malignant tumors that originate within pleural tissue, with epithelioid tumors predominantly comprising its primary pathological subtype. Currently, the combination of pemetrexed and platinum remains the frontline therapeutic strategy for the treatment of MPM. However, recent advancements in the field of immune checkpoint inhibitors have redirected the research spotlight towards the intricate immune microenvironment of MPM. Selenium (Se), a vital trace element, plays pivotal roles in both antitumor and immunoregulation. This study delves into Se nanoparticles (SeNPs) and their functionalized derivatives, specifically lentinan-functionalized SeNPs (LET-SeNPs), with the aim of exploring their potential applications in the treatment of MPM. To tackle the challenge posed by pleural effusion (PE) in malignant pleural mesothelioma (MPM-PE), PE and peripheral blood samples were meticulously collected from MPM patients and subjected to processing utilizing LET-SeNPs. By evaluating the influence of low-energy transfer LET-SeNPs on lymphocytes, we observed an enhanced sensitivity of MPM to natural killer (NK) cells that were pretreated with LET-SeNPs. LET-SeNPs could activate NK92 cells in advance through the TrxR1-pSTAT3 pathway, and further enhance the toxic effect on MPM cells through the interaction of NKG2D-NKG2DL. This process has shown a powerful effect in reducing the invasiveness of MPM and enhancing its penetration and killing efficiency. This finding provides novel therapeutic insights and potential strategies for the treatment of patients with MPM.