Relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy and conventional fractionation radiotherapy in non-small cell lung Cancer

Abstract

Background The effect of brachytherapy on lymphocytes and cytokines in the tumor microenvironment is unclear. This study aimed to analyze the relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy (SBHFRT) and conventional fractionation radiotherapy (CFRT) in non-small cell lung cancer (NSCLC). Methods Lewis tumor-bearing mice were randomly divided into control, CFRT, and SBHFRT groups. On days 7 and 14 after radiation, the expression levels of CD86+, CD4+, CD8+, and Foxp3+ cells, and levels of Ki-67+ protein were detected by immunohistochemistry, and the tumor necrosis rate was calculated. Following this, the levels of interleukin-10 (IL-10), IL-12, and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay. The apoptosis rate was evaluated via flow cytometry. The tumor volume and tumor growth inhibition rate (TGIR) were calculated on day 14. Tumor metabolism was assessed via 18F-FDG micropositron emission tomography/computer tomography. Results The tumor volume reduced by 22.0% and TGIR increased by 92.2% (p < 0.05) in the SBHFRT group. Further, on days 7 and 14 after radiation, tumor metabolism, Ki-67+ and Foxp3+ expression levels, and IL-10 levels were lower, and tumor necrosis and apoptosis rates; CD86+, CD4+, and CD8+ expression levels; and IL-12 and IFN-γ levels were higher in the SBHFRT group than in the CFRT group, particularly on day 7. Conclusion SBHFRT could lead to more accumulation of dendritic cells, anti-tumor lymphocytes, and cytokines, and further reduce the aggregation of immunosuppressive lymphocytes and cytokines in the tumor microenvironment compared with CFRT, and the difference was the most obvious on day 7 after radiation. The clinical significance of the findings remains to be further verified.

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