Experimental study of anti-tumor immunologic response functions after combined treatment of cryoablation with GM-CSF for colorectal cancer liver metastases
10.3760/cma.j.cn112138-20241115-00757
- VernacularTitle:冷冻联合粒细胞-巨噬细胞集落刺激因子对结直肠癌肝转移小鼠抗肿瘤免疫反应的研究
- Author:
Junfeng WANG
1
;
Zhi GUO
Author Information
1. 天津医科大学附属肿瘤医院结直肠肿瘤科，天津300060
- Publication Type:Journal Article
- Keywords:
Colorectal neoplasms;
Neoplasm metastasis;
Cryotherapy;
Immunity
- From:
Chinese Journal of Internal Medicine
2025;64(7):670-674
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To assess the anti-tumor immune response after combined cryoablation and granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment.Methods:A mouse model of colorectal liver metastases (CLM) was established using 80 BALB/c mice. All tumor-bearing mice were divided into a control group ( n=20), a GM-CSF group ( n=20), a cryoablation group ( n=20), and a cryoablation+GM-CSF group ( n=20). Cryoablation was applied using a 1.7-mm diameter cryosurgery needle from an argon-helium cryosurgery system. Tumor size and survival time were observed. Changes in the number of dendritic cells (DCs) in tumors were assessed by immunohistochemistry. Serum cytokine (IFN-γ, IL-4) levels were analyzed by enzyme-linked immunosorbent assay (ELISA), and the Th1/Th2 ratio was estimated from the IFN-γ/IL-4 ratio. One-way analysis of variance was used for data analysis. Results:Our findings showed that combining cryoablation and GM-CSF synergistically increased infiltrating DC numbers. Among the four groups, cryoablation+GM-CSF group exhibited the highest DC count post-treatment (control group: 1.4±0.5/HPF, GM-CSF group: 15.3±1.8/HPF, cryoablation group: 9.6±1.5/HPF, cryoablation+GM-CSF group:17.4±1.3/HPF; F=138.60, P<0.05). Cryoablation, alone or combined with GM-CSF, elevated serum IFN-γ and reduced serum IL-4. IFN-γ levels of cryoablation group increased from 45.6±2.4 pg/ml to 57.8±3.3 pg/ml, F=170.09, P<0.05,and IFN-γ levels of cryoablation+GM-CSF group increased from 45.6±2.4 pg/ml to 86.3±1.9 pg/ml, F=664.31, P<0.05;and IL-4 levels of cryoablation group decreased from 7.21±0.63 pg/ml to 6.35±0.25 pg/ml, F=5.77, P<0.05,IL-4 levels of cryoablation+GM-CSF group decreased from 7.21±0.63 pg/ml to 6.42±0.21 pg/ml, F=10.93, P<0.05. Conversely, GM-CSF alone decreased serum IFN-γ and increased serum IL-4. Notably, combined cryoablation and GM-CSF significantly boosted Th1/Th2 ratios (cryoablation+GM-CSF group: from 6.32±0.45 to 13.43±0.64; F=379.95, P<0.05). Conclusion:Combined cryoablation with GM-CSF treatment exerted a promising anti-tumor immune effect in the treatment of colorectal cancer liver metastases. This approach increased the number of DCs in the tumor microenvironment and improved the anti-tumor immunologic response in tumor-bearing mice.
