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image of Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung Cancer-bearing Mice
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Abstract

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, single-target-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.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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/content/journals/cgt/10.2174/0115665232407110251015103908
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Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung Cancer-bearing Mice
Bentham Science Publishers ; https://doi.org/10.2174/0115665232407110251015103908
/content/journals/cgt/10.2174/0115665232407110251015103908
/content/journals/cgt/10.2174/0115665232407110251015103908
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  • Article Type:     Research Article
Keywords: IL-21 ; siRNA ; Lung cancer ; immunotherapy ; CCR2 ; plasmid

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