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在临床前模型中,运动可减轻免疫抑制并减缓乳腺癌进展。

Exercise reduces immune suppression and breast cancer progression in a preclinical model.

作者信息

Wennerberg Erik, Lhuillier Claire, Rybstein Marissa D, Dannenberg Kyle, Rudqvist Nils-Petter, Koelwyn Graeme J, Jones Lee W, Demaria Sandra

机构信息

Department of Radiation Oncology, Weill Cornell Medical College, Stich Radiation Oncology, New York, NY, USA.

These authors contributed equally to this work.

出版信息

Oncotarget. 2020 Jan 28;11(4):452-461. doi: 10.18632/oncotarget.27464.

Abstract

Exercise is associated with favorable changes in circulating immune cells and improved survival in early-stage breast cancer patients, but the mechansims remain to be fully elucidated. Preclinical studies indicate that physical activity started before tumor injection reduces tumor incidence and progression. Here we tested whether exercise has anti-tumor effects in mice with established 4T1 mammary carcinoma, a mouse model of triple negative breast cancer. Exercise slowed tumor progression and reduced the tumor-induced accumulation of myeloid-derived suppressor cells (MDSCs). The reduction in MDSCs was accompanied by a relative increase in natural killer and CD8 T cell activation, suggesting that exercise restores a favorable immune environment. Consistently, exercise improved responses to a combination of programmed cell death protein 1 (PD-1) blockade and focal radiotherapy. These data support further investigations of exercise in breast cancer patients treated with combinations of immunotherapy and cytotoxic agents to improve cancer outcomes.

摘要

运动与循环免疫细胞的有益变化以及早期乳腺癌患者生存率的提高相关,但其中的机制仍有待充分阐明。临床前研究表明,在肿瘤接种前开始的体力活动可降低肿瘤发生率和进展。在此,我们测试了运动对已建立4T1乳腺癌(三阴性乳腺癌的小鼠模型)的小鼠是否具有抗肿瘤作用。运动减缓了肿瘤进展,并减少了肿瘤诱导的髓源性抑制细胞(MDSC)的积累。MDSC的减少伴随着自然杀伤细胞和CD8 T细胞活化的相对增加,这表明运动可恢复有利的免疫环境。同样,运动改善了对程序性细胞死亡蛋白1(PD-1)阻断和局部放疗联合治疗的反应。这些数据支持进一步研究运动对接受免疫疗法和细胞毒性药物联合治疗的乳腺癌患者的影响,以改善癌症治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80d9/6996907/027cc9850da2/oncotarget-11-452-g001.jpg

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