运动调节 NSCLC 和非荷瘤肺中肥胖诱导的免疫功能障碍：对肺癌治疗和拦截的意义
Exercise Modulates Adiposity-induced Immune Dysfunction in NSCLC and Non-tumor-Bearing Lungs: Implications for Lung Cancer Therapy and Interception.
作者
作者单位
- Department of Thoracic Surgery.
- Department of Cancer Prevention and Control.
- Department of Immunology.
- Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
摘要
中文
确定体力活动是否调节肺和肿瘤微环境中肥胖驱动的免疫抑制以恢复抗肿瘤免疫。肥胖与免疫功能障碍相关，支持肺癌进展，即细胞毒性 T 细胞活性降低和抑制性细胞群扩张。这些改变扩展到肺，即新发和转移性肿瘤的部位。虽然运动改善代谢和炎症特征，但其对这些区域中肥胖相关免疫失调的影响仍不清楚。肥胖和瘦弱小鼠在久坐条件或使用运动轮的条件下植入 Lewis 肺癌。通过 RNA 测序和流式细胞术评估运动对肿瘤和浸润白细胞的影响。还通过流式细胞术表征了有或没有运动的肥胖和瘦弱未荷瘤小鼠的肺，以及来自按总脂肪面积和体力活动分层并进行多变量调整的患者（n = 73）的支气管肺泡灌洗样本。允许自愿运动的肥胖小鼠在肿瘤和肺中表现出较不明显的 Tregs 和潜在抑制性髓系细胞增强，以及较少的 CD8⁺ T 细胞缺陷。这些小鼠表现出显著的肿瘤生长延迟，而在瘦弱小鼠中看到的效果较弱。与改变的血管和代谢程序一致的转录组调节在活跃的肥胖小鼠中也很明显。在人类支气管肺泡灌洗中，体力活动也与肥胖增强的 PD-1⁺ Tregs 和抑制性髓系细胞的减少相关。运动可能逆转肺和肿瘤微环境中肥胖相关的免疫抑制，以补充肺癌拦截和治疗策略。
English
To determine whether physical activity modulates adiposity-driven immune suppression in the lung and tumor microenvironment to restore antitumor immunity. Obesity is associated with immune dysfunction that supports lung cancer progression, namely reduced cytotoxic T-cell activity and expansion of suppressor populations. These alterations extend to the lung, the site of new and metastatic tumors. Although exercise improves metabolic and inflammatory profiles, its impact on adiposity-associated immune dysregulation in these compartments remains unclear. Obese and lean mice were implanted with Lewis lung carcinomas under sedentary conditions or with exercise wheel access. Exercise effects on the tumor and infiltrating leukocytes were assessed by RNA sequencing and flow cytometry. The lungs of obese and lean tumor-naïve mice with and without exercise were also characterized by flow, as were bronchoalveolar lavage samples from patients (n = 73) stratified by total fat area and physical activity with multivariable adjustments. Obese mice allowed voluntary exercise displayed less profound enhancement of Tregs and potentially suppressive myeloid cells and fewer CD8⁺ T-cell deficits in the tumor and lung. These mice displayed significant delays in tumor growth, while muted effects were seen in lean mice. Transcriptomic modulation consistent with altered vascular and metabolic programs was also evident in active obese mice. In human bronchoalveolar lavage, physical activity was also linked to reductions in PD-1⁺ Tregs and suppressive myeloid cells enhanced by adiposity. Exercise may reverse adiposity-associated immune suppression in the lung and tumor microenvironments to complement lung cancer interception and treatment strategies.
分类与指标
- 研究类型
- 基础研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 7.4
- 新锐分区
- 1区