Tumor growth is slowed in mice housed at thermoneutral temperatures (30 to 31°C).
Major finding: Tumor growth is slowed in mice housed at thermoneutral temperatures (30 to 31°C).
Concept: Cold stress induced at standard housing temperatures (20 to 26°C) may suppress antitumor immunity.
Impact: Ambient temperatures should be considered when modeling cancer and responses to therapy in mice.
To ensure the comfort of animal care technicians and reduce the need for frequent cage cleaning, the National Research Council mandates that mice be housed at a constant temperature between 20 and 26°C. In this range, mice can maintain a normal body temperature, but thermogenesis is required because basal metabolism is only sufficient to maintain normal body temperature at 30 to 31°C (a state known as thermoneutrality). Concerned that chronic cold stress caused by standard, subthermoneutral housing temperatures might affect outcomes of in vivo experiments, Kokolus and colleagues compared tumor formation, growth, and metastasis in several commonly used mouse models housed at either standard temperature (approximately 22 to 23°C) or thermoneutral temperature (approximately 30 to 31°C). Remarkably, the tumor growth rate and metastatic burden of mice housed at thermoneutral temperature were significantly reduced compared with those housed at standard temperature. In contrast, differences in tumor growth were not observed in immunodeficient mice, suggesting that subthermoneutral temperatures may affect antitumor immune responses. Indeed, fewer active cytotoxic CD8+ T cells were found in the tumor microenvironment and more immunosuppressive myeloid-derived suppressor cells were observed in the spleen at standard temperature than at thermoneutral temperature. At standard temperature, but not thermoneutral temperature, the body temperature of mice bearing large tumors also fell by 1 to 2 degrees, indicating that tumor growth impairs thermoregulation under subthermoneutral conditions. Moreover, unlike tumor-free mice, which preferred thermoneutral temperature over standard temperature in a temperature preference assay, tumor-bearing mice preferred the warmest temperature available (38°C), an example of heat-seeking behavior consistent with elevated cold stress and an increased requirement for thermogenesis. Collectively, these findings raise the possibility that at standard animal housing temperatures, murine tumor model experiments are performed in the context of cold stress–induced metabolic changes and immunosuppression and may not accurately model antitumor immune responses.