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Comparing thermal stress reduction strategies that influence MDSC accumulation in tumor bearing mice
Cellular Immunology ( IF 3.7 ) Pub Date : 2021-01-09 , DOI: 10.1016/j.cellimm.2021.104285
Cameron MacDonald 1 , Samuel Ministero 1 , Manu Pandey 2 , Denisha Robinson 1 , Evan Forti Hong 1 , Bonnie Hylander 1 , Philip McCarthy 2 , Christopher Gordon 3 , Elizabeth Repasky 1 , Hemn Mohammadpour 1
Affiliation  

Myeloid derived suppressor cells (MDSCs) are a diverse collection of immune cells that suppress anti-tumor immune responses. Decreasing MDSCs accumulation in the tumor microenvironment could improve the anti-tumor immune response and improve immunotherapy. Here, we examine the impact of physiologically relevant thermal treatments on the accumulation of MDSCs in tumors in mice. We found that different temperature-based protocols, including 1) weekly whole-body hyperthermia, 2) housing mice at their thermoneutral temperature (TT, ~30 °C), and 3) housing mice at a subthermoneutral temperature (ST,~22 °C) while providing a localized heat source, each resulted in a reduction in MDSC accumulation and improved tumor growth control compared to control mice housed at ST, which is the standard, mandated housing temperature for laboratory mice. Additionally, we found that low dose β-adrenergic receptor blocker (propranolol) therapy reduced MDSC accumulation and improved tumor growth control to a similar degree as the models that relieved cold stress. These results show that thermal treatments can decrease MDSC accumulation and tumor growth comparable to propranolol therapy.



中文翻译:


比较影响荷瘤小鼠 MDSC 积累的热应激减少策略



骨髓源性抑制细胞 (MDSC) 是抑制抗肿瘤免疫反应的多种免疫细胞集合。减少肿瘤微环境中MDSC的积累可以改善抗肿瘤免疫反应并改善免疫治疗。在这里,我们研究了生理相关的热处理对小鼠肿瘤中 MDSC 积累的影响。我们发现不同的基于温度的方案,包括 1) 每周全身热疗,2) 将小鼠饲养在热中性温度(TT,~30°C),3)将小鼠饲养在亚热中性温度(ST,~22°C) C)在提供局部热源的同时,与饲养在 ST 中的对照小鼠相比,每种热源都导致 MDSC 积累减少并改善肿瘤生长控制,ST 是实验室小鼠的标准规定饲养温度。此外,我们发现低剂量 β-肾上腺素受体阻滞剂(普萘洛尔)治疗可减少 MDSC 积累并改善肿瘤生长控制,其程度与缓解冷应激的模型相似。这些结果表明,与普萘洛尔疗法相当,热处理可以减少 MDSC 积累和肿瘤生长。

更新日期:2021-01-20
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