Thermoneutrality, mice, and cancer: a heated opinion

Hylander, Bonnie L.; Repasky, Elizabeth A.

doi:10.1016/j.trecan.2016.03.005

Cited by 107Cancer, Stress, Anesthesia, and Immune ResponseAnimal testing and alternativesEffects of Environmental Stressors on Livestock

Thermoneutrality, mice, and cancer: a heated opinion

Hylander, Bonnie L., Repasky, Elizabeth A.·2016·Trends in cancer

DOI 10.1016/j.trecan.2016.03.005

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Abstract

The 'mild' cold stress caused by standard sub-thermoneutral housing temperatures used for laboratory mice in research institutes is sufficient to significantly bias conclusions drawn from murine models of several human diseases. We review the data leading to this conclusion, discuss the implications for research and suggest ways to reduce problems in reproducibility and experimental transparency caused by this housing variable. We have found that these cool temperatures suppress endogenous immune responses, skewing tumor growth data and the severity of graft versus host disease, and also increase the therapeutic resistance of tumors. Owing to the potential for ambient temperature to affect energy homeostasis as well as adrenergic stress, both of which could contribute to biased outcomes in murine cancer models, housing temperature should be reported in all publications and considered as a potential source of variability in results between laboratories. Researchers and regulatory agencies should work together to determine whether changes in housing parameters would enhance the use of mouse models in cancer research, as well as for other diseases. Finally, for many years agencies such as the National Cancer Institute (NCI) have encouraged the development of newer and more sophisticated mouse models for cancer research, but we believe that, without an appreciation of how basic murine physiology is affected by ambient temperature, even data from these models is likely to be compromised.

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Housing temperature influences the pattern of heat shock protein induction in mice following mild whole body hyperthermia
Eng, J. W. ‐., Reed, C. B., Kokolus, K. M., & Repasky, E. A. (2014) · International Journal of Hyperthermia · doi:10.3109/02656736.2014.981300 · Cited by 28 · see citing works
Self-citation
Interactions Between Housing Density and Ambient Temperature in the Cage Environment: Effects on Mouse Physiology and Behavior.
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Cold acclimation-recruited nonshivering thermogenesis: the Syrian hamster is not an exception
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Standard Sub-Thermoneutral Caging Temperature Influences Radiosensitivity of Hematopoietic Stem and Progenitor Cells
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Self-citation
RATE OF GAIN AND LOSS OF COLD RESISTANCE IN MICE
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Mouse reproductive fitness is maintained up to an ambient temperature of 28℃ when housed in individually-ventilated cages
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Body temperature regulation
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Temperature matters with rodent metabolic studies
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Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
β-Adrenergic Signaling in Mice Housed at Standard Temperatures Suppresses an Effector Phenotype in CD8+ T Cells and Undermines Checkpoint Inhibitor Therapy
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Self-citation
A Neuroscientist’s Guide to the Vole
Kenkel, W. M., Gustison, M. L., & Beery, A. K. (2021) · Current Protocols · doi:10.1002/cpz1.175 · Cited by 52 · see citing works

Authors: Hylander, B. L., & Repasky, E. A.
Affiliations: Roswell Park Comprehensive Cancer Center (US)
Corresponding author: Repasky, Elizabeth A.
ORCID: Hylander, Bonnie L.
Repasky, Elizabeth A.
Venue: Trends in cancer
Publisher: Elsevier BV
Published: 2016-04
Volume: 2
Issue: 4
Pages: 166-175
ISSN: 2405-8025 (ISSN-L)
2405-8033
DOI: 10.1016/j.trecan.2016.03.005
OpenAlex: W2343236286
Cited by: 107
References: 97
Citations by year: 2026: 5 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 15 · 2021: 15 · 2020: 16 · 2019: 8 · 2018: 14 · 2017: 8 · 2016: 2
FWCI: 1.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in cancer (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute on Aging (R03AG049489)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Effects of Environmental Stressors on Livestock
Keywords: thermoneutrality, cold stress, mouse tumor model, tumor growth, graft-versus-host disease, immunosuppression, energy homeostasis, adrenergic stress, reproducibility, experimental variability, ambient temperature effects
MeSH terms: Animals, Disease Susceptibility, Drug Evaluation, Preclinical, Housing, Animal, Metabolic Diseases, Neoplasms, Stress, Physiological, Temperature, Thermosensing, Immunocompromised Host, Treatment Outcome, Apoptosis, Mice

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Thermoneutrality, mice, and cancer: a heated opinion

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