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Exercise Modulates Polarization of TAMs and Expression of Related Immune Checkpoints in Mice with Lung Cancer

Journal of cancer(2022)

Shenzhen Univ | Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education

Cited 4|Views4
Abstract
Purpose: Many studies have found that both endurance exercise (EX) and high-intensity interval training (HIIT) have a positive therapeutic effect on the treatment of lung cancer patients, but the specific mechanism is unclear. Therefore, we investigated whether EX and HIIT could delay the progression of lung cancer by affecting the infiltration of tumor-associated macrophages (TAMs) and restoring the tumor phagocytic activity of TAMs in lung cancer tissue. Methods: BALB/c mice were divided into 4 groups. The mice were given saline as the saline group (Saline), and the mice were given urethane as the lung cancer mice. The lung cancer mice were randomly divided into the control group (CON), EX group, and HIIT group. After exercise, the cancer tissues were collected for RT-PCR, immunofluorescence staining, and Wes automated western blotting system analysis. Results: Compared with the Saline group, the mRNA levels of TAMs M1 markers IL-6, TNF-α, iNOS, and M2 markers CD206, IL-10, and Arg-1 in the CON group were significantly increased (P<0.05). There was no significant difference in the percentage of F4/80 positive cells among the groups. Compared with the CON group, the percentage of CD86-positive cells in TAMs in the EX group was significantly decreased (P<0.05). From the protein expression level, compared with the CON group, the expression of SIRPα in the EX group was significantly increased (P<0.0001) and the expression of PD-L1 had a tendency to increase (P=0.06). Compared with the CON group, the expressions of IL-10, IL-12, CD47, and CD24 in the HIIT group were significantly increased (P<0.05). In addition, compared with the CON group, plasma IFN-γ in the EX group and HIIT group was significantly increased (P<0.05). Conclusion: Lung cancer tissue presents an inflammatory tumor microenvironment. The therapeutic effect of exercise on lung cancer is independent of the infiltration of TAMs in lung cancer tissue. In addition, endurance exercise can reduce the proportion of M1-type TAMs in lung cancer tissues, while HIIT antagonistically regulates M1 and M2 polarization of TAMs by increasing the levels of IL-10 and IL-12 in lung cancer tissues and circulating IFN-γ. Finally, endurance exercise and HIIT can modulate the expression of some immune checkpoints in lung cancer tissues.
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exercise,TAMs,PD-L1,CD47,CD24,Lung cancer,IL-10/ 12
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要点】:研究探讨了耐力运动(EX)和高强度间歇训练(HIIT)是否通过影响肺癌组织中的肿瘤相关巨噬细胞(TAMs)浸润及其吞噬活性来延缓肺癌进展,并发现运动可调节部分免疫检查点的表达,具有抗肿瘤作用。

方法】:将BALB/c小鼠分为四组,其中一组作为盐水对照组(Saline),其余三组以尿素诱导生成肺癌模型,并分别设为对照组(CON)、耐力运动组(EX)和高强度间歇训练组(HIIT),通过RT-PCR、免疫荧光染色和Wes自动化Western印迹系统进行分析。

实验】:实验结果表明,与对照组相比,耐力运动组TAMs中M1型细胞的比例下降,SIRPα蛋白表达显著增加,PD-L1表达有升高趋势;高强度间歇训练组IL-10、IL-12、CD47和CD24的表达显著增加,两组的血浆IFN-γ水平均显著升高。