Abstract 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.

中文翻译：

---

硒纳米颗粒调节硒蛋白以促进细胞因子诱导的杀伤细胞为基础的癌症免疫治疗

摘要 作为典型的过继细胞转移方式之一，细胞因子诱导杀伤细胞（CIK）介导的免疫疗法在癌症治疗中具有广阔的应用前景。然而，细胞因子诱导的杀伤 (CIK) 细胞在体内的短暂持久性和复杂的肿瘤微环境是基于 CIK 的免疫治疗的主要挑战。在此，我们通过将硒纳米颗粒 (SeNPs) 与 CIK 细胞结合以实现有效的癌症免疫治疗，展示了一种安全有效的策略。有趣的是，SeNPs 可以有效延长 CIK 细胞在外周血中的体内持久性。此外，SeNPs可以通过上调活化受体-NKG2D及其配体的表达，显着增强来自癌症患者的CIK细胞对肿瘤细胞的细胞毒性，同时对CIK和肿瘤细胞没有毒性。一系列证据表明，SeNPs 代谢为硒代半胱氨酸主要有助于其在促进 CIK 治疗方面的独特优势。重要的是，这种策略可以有效地诱导自然杀伤细胞浸润到肿瘤中，并使肿瘤相关巨噬细胞极化为 M1 表型，以触发强大的免疫反应，以对抗涉及肝脏、乳腺和前列腺肿瘤的多种肿瘤进展。该研究为促进CIK疗法在癌症治疗中的临床应用提供了一种新策略。这种策略可以有效地诱导自然杀伤细胞浸润到肿瘤中，并使肿瘤相关巨噬细胞极化为 M1 表型，以触发强大的免疫反应，以对抗涉及肝脏、乳腺和前列腺肿瘤的多种肿瘤进展。该研究为促进CIK疗法在癌症治疗中的临床应用提供了一种新策略。这种策略可以有效地诱导自然杀伤细胞浸润到肿瘤中，并使肿瘤相关巨噬细胞极化为 M1 表型，以触发强大的免疫反应，以对抗涉及肝脏、乳腺和前列腺肿瘤的多种肿瘤进展。该研究为促进CIK疗法在癌症治疗中的临床应用提供了一种新策略。