Tumor growth and anti-tumor immunity depend upon extent of metabolic energy devoted to thermoregulation in laboratory mice (P2099)

Abstract

Abstract Laboratory mice are housed under relatively cool conditions and even though their core temperature remains normal, mice are cold stressed and exhibit significant increases in metabolic heat production. We compared tumor growth in mice housed at a standard ambient temperature (22oC) and at a thermoneutral temperature (30oC) which reduces metabolic effort needed for maintaining core temperature. We found significantly reduced tumor incidence and growth rates in animals housed at thermoneutral vs standard temperature using four different syngeneic tumor models, including a metastasis model. Because this difference was not seen in SCID or NUDE mice or in mice depleted of CD8+ T cells, we suspected that a prominent result of metabolic cold stress is diminished adaptive immunity. Immunohistochemistry and flow cytometry confirmed the presence of more CD8+ T cells (including antigen-specific cells) within the tumor microenvironment and spleens of animals at thermoneutral vs standard temperature. Conversely, animals at standard temperature had significantly increased infiltration of immunosuppressive cell subsets including GR-1+CD11b+ myeloid derived suppressor cells and Foxp3+ cells. These data reveal a fundamental relationship between energy utilized for thermoregulation and CD8+ T cell-dependent immunity and strongly suggest that immunological data collected from tumor bearing mice housed at standard temperature could be significantly biased by chronic cold stress.