Combined exercise intervention in a mouse model of high-risk neuroblastoma: effects on physical, immune, tumor and clinical outcomes.

IF 3.5 4区 医学 Q2 IMMUNOLOGY
Exercise Immunology Review Pub Date : 2023-01-01
Cecilia Rincón-Castanedo, Asunción Martín-Ruiz, Sandra Zazo, Ana L Luis Huertas, Pedro L Valenzuela, María Morán, Steven J Fleck, Alejandro Santos-Lozano, Manuek Ramírez, Federico Rojo, Alejandro Lucia, África González-Murillo, Carmen Fiuza-Luces
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引用次数: 0

Abstract

Background: Exercise might exert anti-tumoral effects in adult cancers but this question remains open in pediatric tumors, which frequently show a different biology compared to adult malignancies. We studied the effects of an exercise intervention on physical function, immune variables and tumoral response in a preclinical model of a highly aggressive pediatric cancer, high-risk neuroblastoma (HR-NB).

Methods: 6-8-week-old male mice with orthotopically-induced HR-NB were assigned to a control (N = 13) or exercise (5-week combined [aerobic+resistance]) group (N = 17). Outcomes included physical function (cardiorespiratory fitness [CRF] and muscle strength), as well as related muscle molecular indicators, blood and tumor immune cell and molecular variables, tumor progression, clinical severity, and survival.

Results: Exercise attenuated CRF decline (p=0.029 for the group-by-time interaction effect), which was accompanied by higher muscle levels of oxidative capacity (citrate synthase and respiratory chain complexes III, IV and V) and an indicator of antioxidant defense (glutathione reductase) in the intervention arm (all p≤0.001), as well as by higher levels of apoptosis (caspase-3, p=0.029) and angiogenesis (vascular endothelial growth factor receptor-2, p=0.012). The proportion of 'hot-like' (i.e., with viable immune infiltrates in flow cytometry analyses) tumors tended to be higher (p=0.0789) in the exercise group (76.9%, vs. 33.3% in control mice). Exercise also promoted greater total immune (p=0.045) and myeloid cell (p=0.049) infiltration within the 'hot' tumors, with a higher proportion of two myeloid cell subsets (CD11C+ [dendritic] cells [p=0.049] and M2-like tumor-associated macrophages [p=0.028]), yet with no significant changes in lymphoid infiltrates or in cirulating immune cells or chemokines/cytokines. No training effect was found either for muscle strength or anabolic status, cancer progression (tumor weight and metastasis, tumor microenvironment), clinical severity, or survival.

Conclusions: Combined exercise appears as an effective strategy for attenuating physical function decline in a mouse model of HR-NB, also exerting some potential immune benefits within the tumor, which seem overall different from those previously reported in adult cancers.

联合运动干预高风险神经母细胞瘤小鼠模型:对身体、免疫、肿瘤和临床结果的影响
背景:运动可能在成人癌症中发挥抗肿瘤作用,但这个问题在儿童肿瘤中仍然存在,与成人恶性肿瘤相比,儿童肿瘤经常表现出不同的生物学特性。我们研究了运动干预对高侵袭性儿童癌症高危神经母细胞瘤(HR-NB)的身体功能、免疫变量和肿瘤反应的影响。方法:将6-8周龄原位诱导HR-NB雄性小鼠分为对照组(N = 13)和运动组(5周[有氧+阻力]联合组)(N = 17)。结果包括身体功能(心肺功能[CRF]和肌肉力量),以及相关的肌肉分子指标,血液和肿瘤免疫细胞和分子变量,肿瘤进展,临床严重程度和生存。结果:运动减轻了CRF的下降(按时间分组的相互作用效应p=0.029),同时干预组肌肉的氧化能力(柠檬酸合成酶和呼吸链复合物III、IV和V)和抗氧化防御指标(谷胱甘肽还原酶)水平升高(均p≤0.001),以及细胞凋亡(caspase-3, p=0.029)和血管生成(血管内皮生长因子受体-2,p=0.012)水平升高。运动组“热样”(即流式细胞术分析中存在存活的免疫浸润)肿瘤的比例往往更高(p=0.0789)(76.9%,对照小鼠为33.3%)。运动还促进了“热”肿瘤内更大的总免疫细胞(p=0.045)和髓细胞(p=0.049)浸润,两种髓细胞亚群(CD11C+[树突状]细胞[p=0.049]和m2样肿瘤相关巨噬细胞[p=0.028])的比例更高,但淋巴细胞浸润或循环免疫细胞或趋化因子/细胞因子没有显著变化。没有发现训练对肌肉力量或合成代谢状态、癌症进展(肿瘤重量和转移、肿瘤微环境)、临床严重程度或生存有影响。结论:在HR-NB小鼠模型中,联合运动似乎是一种有效的减轻身体功能下降的策略,也在肿瘤中发挥了一些潜在的免疫益处,这似乎与先前在成人癌症中报道的总体不同。
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来源期刊
Exercise Immunology Review
Exercise Immunology Review 医学-免疫学
CiteScore
16.00
自引率
0.00%
发文量
7
期刊介绍: Exercise Immunology Review (EIR) serves as the official publication of the International Society of Exercise and Immunology and the German Society of Sports Medicine and Prevention. It is dedicated to advancing knowledge in all areas of immunology relevant to acute exercise and regular physical activity. EIR publishes review articles and papers containing new, original data along with extensive review-like discussions. Recognizing the diverse disciplines contributing to the understanding of immune function, the journal adopts an interdisciplinary approach, facilitating the dissemination of research findings from fields such as exercise sciences, medicine, immunology, physiology, behavioral science, endocrinology, pharmacology, and psychology.
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