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Oncology Times:
doi: 10.1097/01.COT.0000444903.03870.16
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Possible Explanation for Conflicting Results of Cancer Studies in Mouse Models

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The temperature at which laboratory mouse models are housed may induce mild cold stress sufficient to increase cancer cell growth by interfering with immune protection, according to a provocative study published in Proceedings of the National Academy of Sciences (doi: 10.1073/pnas.1304291110). The findings could hold implications for a vast number of preclinical studies in mouse models, the researchers said.

“We learned through this research that cold stress is a very potent effector of mouse physiology, mostly because mice lose heat quite easily compared with humans,” study coauthor Elizabeth Repasky, PhD, the Dr. William Huebsch Professor in Immunology at Roswell Park Cancer Institute, said in a news release. “Our study shows that enduring even mild cold stress blocks strong immunity against cancer.”

She and her colleagues analyzed tumor formation, growth rate, and metastasis in several common mouse models of cancer, comparing animals housed at standard temperature (22–23°C) with animals housed at thermoneutral temperature (30–31°C). Even though the lower temperature falls within the current standard range (20–26°C/68–78.8°F) mandated in guidelines by the National Research Council, the lower temperatures were shown to induce suppression of the antitumor immune response and promote tumor growth and metastasis.

The findings suggest that investigating mouse models under a single set of environmental temperature conditions may lead to a misunderstanding of the antitumor immune potential, the researchers said.

“The differences in tumor growth imposed on cold-stressed mice could mean that an investigational treatment such as an immunotherapy agent might appear to work better than it actually does or, conversely, it could be that the introduction of cold stress inhibits the ability of the medication to work.”

And, the data highlight the need for additional research to determine how systemic metabolic stress modulates the functions of immune effector cells, particularly in tumor-bearing mice, and whether cancer therapies, including immunotherapy, are affected by the housing temperature.

Wolters Kluwer Health | Lippincott Williams & Wilkins

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