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Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung
Jing Li1,2, Kun Li3, Jinhua Yang4
1Key Laboratory of Medical Laboratory, Henan Provincial Chest Hospital, Affiliated Chest Hospital of Zhengzhou University, Zhengzhou, China.
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.
Insights
Combining CCR2 blockade with IL-21 therapy shows synergistic anti-lung-cancer effects. This dual approach inhibits tumor growth and boosts the immune response, offering a promising new strategy for lung cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Lung cancer necessitates novel therapeutic strategies.
- Single-target therapies often prove insufficient, highlighting the need for multi-target approaches.
- Interleukin-21 (IL-21) demonstrates anti-tumor activity, but its combination with CCR2-targeted therapy for lung cancer requires investigation.
Purpose of the Study:
- To evaluate the combined anti-tumor efficacy of CCR2 blockade and IL-21 in a mouse lung cancer model.
- To investigate the impact of this combination therapy on tumor cell proliferation, immune cell infiltration, and overall anti-tumor immune response.
Main Methods:
- Utilized mouse Lewis lung cancer cells and an IL-21-siRNA-CCR2 plasmid.
- Assessed apoptosis, immune cell populations, protein expression, and proliferation using Annexin V-FITC, flow cytometry, Western blot, Ki67 IHC, immunofluorescence, and TUNEL assays.
Main Results:
- Combination therapy significantly inhibited CCR2 expression and tumor growth while enhancing IL-21 expression.
- Increased infiltration of CD4+ and CD8+ T lymphocytes within tumor tissues was observed.
- The treatment promoted M1 macrophage polarization, reduced M2 macrophages, and increased CD4+ T lymphocytes and NK cells in spleen.
Conclusions:
- Combined IL-21 and CCR2 blockade demonstrates a synergistic anti-lung-cancer effect.
- This combination therapy suppresses tumor cell proliferation and enhances the host's anti-tumor immune response.
- Further studies will explore the efficacy of this combination across diverse tumor cell lines.
