CELL INTELLIGENCE · 肿瘤细胞治疗研究

INTRODUCTION: There is an urgent and ongoing need to develop effective therapeutic strategies for lung cancer. CCR2 is considered a valid target for lung cancer treatment. However, singletarget- oriented monotherapy frequently fails to yield satisfactory results, and multi-target therapy has become the current trend. IL-21 exerts anti-tumor effects across various cancers, including lung cancer. Whether the combination of CCR2-targeted therapy and IL-21 exerts a stronger anti-tumor effect remains to be verified. METHODS: Mouse Lewis lung cancer cells and pre-constructed IL-21-siRNA-CCR2 plasmid were used. Annexin V-FITC, flow cytometry, Western blot, Ki67 IHC, immunofluorescence, and TUNEL assay were used to analyze apoptosis, immune cells, proteins, and proliferation. RESULTS: Compared with single-agent treatments, combination treatment significantly inhibited CCR2 expression, enhanced IL-21 expression, and slowed tumor growth in mouse lung cancer tissues. Further analysis demonstrated that this treatment effectively increased the infiltration of CD4⁺ and CD8⁺ T lymphocytes in tumor tissues, elevated the proportion of M1 macrophages while reducing that of M2 macrophages, and notably increased the percentages of CD4+ T lymphocytes and NK cells in mouse spleens. DISCUSSION: The combination treatment not only directly suppressed the proliferation of tumor cells but also enhanced the overall anti-tumor immune response in tumor-bearing mice. In subsequent studies, it will be further verified that the efficacy of this treatment is in a variety of tumor cell lines. CONCLUSION: The combination of IL-21 and CCR2 blockade exerts a synergistic anti-lung-cancer effect.