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Monday, December 9, 2013

Temperature matters for mouse tumors

Animal models are enormously useful. Whether you’re studying concussions in flies or the progression of death in nematode worms, you can learn many things that are applicable to humans without actually harming any humans. For example, cancer therapies rely heavily on mouse models. There’s just one problem. The way the mice are housed may be affecting the data.

In most facilities, lab mice are kept at 2026°C (6879°F). This is very comfortable for the animal care technicians in their lab coats, but not so much for the mice, who prefer a balmy 30°C (86°F). This means that the mice are under a constant state of cold stress. Nobody thought much about this, since the mice seemed to be coping fine. However, as Kathleen Kokolus and her colleagues from the Roswell Park Cancer Institute found, coping and thriving are two different things, especially when it comes to cancer.

The researchers compared tumor formation and growth in mice housed at either 22°C or 30°C. After allowing the mice to acclimate to their maintenance temperature, the mice were injected with one of four types of tumor cells. Each type of tumor grew more rapidly in the cold mice than in the warm mice. The tumors also metastasized to the lungs more quickly at the colder temperature. When mice were allowed to move between cages set at different temperatures, healthy mice spent most of their time at 30°C, whereas tumor-bearing mice preferred 38°C, the warmest choice available to them.

Caption: Lab mice huddling in a cage.
Credit: Image courtesy of Kathleen Kokolus and Sandra Sexton.

Further tests implicated cytotoxic T cells (or CD8+ T cells) in delaying the growth and metastasis of tumors. Cytotoxic T cells are responsible for killing cells that have been damaged by infection or cancer, and there were more of these immune cells present at warmer temperatures. When the temperature comparison tests were rerun with immunocompromised mice that can’t make cytotoxic T cells, there was no difference in tumor growth between the warmer and colder mice.

The point of these experiments is not to suggest that human cancer patients should be kept warm (though obviously, people should be made as comfortable as possible). Rather, it’s to point out that unknown or unexpected variables can skew medical tests. This may explain the unfortunately common occurrence of experimentally promising drugs not living up to expectations in human clinical trials.

Kathleen M. Kokolus, Maegan L. Capitano, Chen-Ting Lee, Jason W.-L. Eng, Jeremy D. Waight, Bonnie L. Hylander, Sandra Sexton, Chi-Chen Hong, Christopher J. Gordon, Scott I. Abrams, & Elizabeth A. Repasky (2013). Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1304291110.