一項研究發(fā)現(xiàn),,在多數(shù)動物研究機構(gòu)小鼠生活的地方的溫度可能扭曲癌癥免疫療法研究的結(jié)果,。小鼠天然地尋找溫暖的巢環(huán)境從而讓產(chǎn)熱代謝活動的能量開支最小化,,并且已知健康的小鼠喜愛30到31攝氏度的環(huán)境溫度,。
然而,大多數(shù)動物研究機構(gòu)的實驗室小鼠生活在20到26攝氏度的環(huán)境中,,這部分是為了減少對籠子清潔的要求并且增加技術人員的舒適度,。盡管低于最優(yōu)的溫度導致了輕微的冷壓力,實驗室小鼠通常維持了正常的體溫,。
為了確定這種溫度不一致是否可能影響疾病病程,,Elizabeth Repasky及其同事比較了生活在22-23攝氏度或30-31攝氏度的幾個常見癌癥小鼠模型的腫瘤形成、生長率和轉(zhuǎn)移,。這組作者報告說,,生活在30攝氏度的小鼠的4種不同類型的移植腫瘤比生活在22度的小鼠的腫瘤生長更緩慢,即便這兩組小鼠都維持了正常體溫,。類似地,,致癌物引發(fā)的腫瘤和一個移植的乳腺腫瘤向肺轉(zhuǎn)移在更高溫度生活的小鼠身上得到了更好的控制。
這組作者報告說,,在30攝氏度的這種改善的腫瘤生長控制可能是被適應性免疫應答的相應增加調(diào)控的,,其證據(jù)是殺手淋巴T細胞在腫瘤內(nèi)部增加,而在免疫抑制細胞內(nèi)減少,。這組作者提出,,由于冷壓力可能轉(zhuǎn)移用于產(chǎn)熱的能量,并且抑制抗癌免疫應答,,環(huán)境溫度可能影響實驗室小鼠對實驗性癌癥免疫療法的響應,。(生物谷Bioon.com)
生物谷推薦的英文摘要
Proceedings of the National Academy of the Sciences of the United States of America doi: 10.1073/pnas.1304291110
Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature
Kathleen M. Kokolusa,1, Maegan L. Capitanoa,,1,, Chen-Ting Leea, Jason W.-L. Enga,, Jeremy D. Waighta,, Bonnie L. Hylandera, Sandra Sextonb,, Chi-Chen Hongc,, Christopher J. Gordond, Scott I. Abramsa,, and Elizabeth A. Repaskya,,2
We show here that fundamental aspects of antitumor immunity in mice are significantly influenced by ambient housing temperature. Standard housing temperature for laboratory mice in research facilities is mandated to be between 20–26 °C; however,, these subthermoneutral temperatures cause mild chronic cold stress,, activating thermogenesis to maintain normal body temperature. When stress is alleviated by housing at thermoneutral ambient temperature (30–31 °C), we observe a striking reduction in tumor formation,, growth rate and metastasis. This improved control of tumor growth is dependent upon the adaptive immune system. We observe significantly increased numbers of antigen-specific CD8+ T lymphocytes and CD8+ T cells with an activated phenotype in the tumor microenvironment at thermoneutrality. At the same time there is a significant reduction in numbers of immunosuppressive MDSCs and regulatory T lymphocytes. Notably,, in temperature preference studies, tumor-bearing mice select a higher ambient temperature than non-tumor-bearing mice,, suggesting that tumor-bearing mice experience a greater degree of cold-stress. Overall,, our data raise the hypothesis that suppression of antitumor immunity is an outcome of cold stress-induced thermogenesis. Therefore, the common approach of studying immunity against tumors in mice housed only at standard room temperature may be limiting our understanding of the full potential of the antitumor immune response.