In a study reported in Proceedings of the National Academy of Sciences USA, Kokolusa and colleagues showed that fundamental aspects of antitumor immunity are significantly affected by ambient housing temperature for lab mice.
Standard ambient temperature in research facility lab mice housing is 20°C to 26°C. However, as shown by the investigators, such subthermoneutral temperatures cause chronic mild cold stress, requiring activation of thermogenesis mechanisms to maintain normal body temperature. When cold stress was eliminated by housing mice at a thermoneutral temperature of 30°C to 31°C, there was a dramatic reduction in tumor formation, growth rate, and metastases in tumor models. This greater control of tumor growth was found to be dependent on adaptive immune system activity, with significantly increased numbers of antigen-specific CD8-positive T lymphocytes and activated CD8-positive T cells being found in the tumor microenvironment at thermoneutral temperatures.
Thermoneutrality was also associated with significant reduction in numbers of immunosuppressive myeloid-derived suppressor cells and regulatory T lymphocytes. It was also found that tumor-bearing mice preferentially selected a higher ambient temperature than control mice, suggesting that tumor-bearing mice experience a greater degree of cold stress at a given temperature and seek to avoid it.
The investigators concluded, “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.” ■
Kokolus KM, et al: Proc Natl Acad Sci USA 110:20176-20181, 2013.