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Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature.

ABSTRACT: 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.

SUBMITTER: Kokolus KM

PROVIDER: S-EPMC3864348 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature.

Kokolus Kathleen M KM Capitano Maegan L ML Lee Chen-Ting CT Eng Jason W-L JW Waight Jeremy D JD Hylander Bonnie L BL Sexton Sandra S Hong Chi-Chen CC Gordon Christopher J CJ Abrams Scott I SI Repasky Elizabeth A EA

Proceedings of the National Academy of Sciences of the United States of America 20131118 50

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 tum ...[more]

PMID: 24248371

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Project description:The aim of this study is to investigate if baseline relative peripheral refraction (RPR) influences the myopia control effects in Chinese myopic children wearing Defocus Incorporated Multiple Segments (DIMS) lenses. Peripheral refraction at 10°, 20°, and 30° nasal (10 N, 20 N, 30 N) and temporal (10 T, 20 T, 30 T) retina were measured at six-month intervals for children who participated in a 2-year randomized controlled trial. The relationship between the baseline peripheral refractions and myopia progression and axial length changes were analysed. A total of 79 children and 81 children in the DIMS and single vision (SV) group were investigated, respectively. In the DIMS group, more baseline myopic RPR spherical equivalent (SE) was associated with more myopic progression (10 N: r = 0.36, p = 0.001; 20 N: r = 0.35, p = 0.001) and greater axial elongation (10 N: r = −0.34, p = 0.001; 20 N: r = −0.29, p = 0.006) after adjusting for co-factors. In the SV group, baseline RPR had association with only myopia progression (10 N: r = 0.37, p = 0.001; 20 N: r = 0.36, p = 0.001; 30 N: r = 0.35, p = 0.002) but not with axial elongation after Bonferroni correction (p > 0.008). No statistically significant relationship was found between temporal retina and myopia progression or axial elongation in both groups. Children with baseline myopic RPR had statistically significant more myopia progression (mean difference around −0.40 D) and more axial elongation (mean difference 0.15 mm) when compared with the children having baseline hyperopic RPR in the DIMS group but not in the SV group. In conclusion, the baseline RPR profile may not influence future myopia progression or axial elongation for the SV lens wearers. However, DIMS lenses slowed down myopia progression and was better in myopia control for the children with baseline hyperopic RPR than the children with myopic RPR. This may partially explain why myopia control effects vary among myopic children. Customised myopic defocus for individuals may optimise myopia control effects, and further research to determine the optimal dosage, with consideration of peripheral retinal profile, is warranted.

Dataset Information

Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature.

Publications

Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature.

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