Selenium nanoparticles regulates selenoprotein to boost cytokine-induced killer cells-based cancer immunotherapy

SeNPs could regulate selenoproteins to boost CIK-based immunotherapy via improving the in vivo persistence of CIK cells and regulate the interaction between patient-derived CIK cells and tumor cells. [Display omitted] •Selenium nanoparticles (SeNPs) can effectively prolong the in vivo persistence of CIK cells.•SeNPs maximize the interactions between CIK and tumour cells by upregulating NKG2D and its ligands.•SeNPs metabolism into selenocystine mainly contributes to its synergistic effects with CIK cells.•This strategy can effectively induce robust immunities via shaping microenvironment to combat multiple tumours progression. As one of the typical adoptive cell transfer modality, cytokine-induced killer cell (CIK)-mediated immunotherapy exhibits promising applications in cancer treatment. However, the short in vivo persistence of cytokine-induced killer (CIK) cells and complex tumour microenvironment are major challenges for CIK-based immunotherapy. Herein, we demonstrate a safe and effective strategy by combining selenium nanoparticles (SeNPs) with CIK cells for efficient cancer immmunotherapy. Intriguingly, SeNPs could effectively prolong the in vivo persistence of CIK cells in peripheral blood. Furthermore, SeNPs can significantly enhance the cytotoxicity of CIK cells from cancer patients to tumour cells through upregulating the expressions of activation receptor-NKG2D and its ligands, while exhibiting no toxicity to CIK and tumor cells. Series of evidences indicate that SeNPs metabolism into selenocystine mainly contributes to its unique advantages in facilitating CIK treatment. Importantly, this strategy can effectively induce natural killer cells infiltrating in tumours and shape tumour-associated macrophages polarizing into M1 phenotype to trigger robust immune responses for combating multiple tumours progression involving hepatic, breast and prostate ones. This study provides a novel strategy to promote the clinical applications of CIK therapy in cancer treatment.