title: Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature.
abstract: We show here that fundamental aspects of antitumor immunity in mice are significantly influenced by ambient housing temperature. Standard housing temperature for laboratory mice in research facilities is mandated to be between 20-26 °C; however, these subthermoneutral temperatures cause mild chronic cold stress, activating thermogenesis to maintain normal body temperature. When stress is alleviated by housing at thermoneutral ambient temperature (30-31 °C), we observe a striking reduction in tumor formation, growth rate and metastasis. This improved control of tumor growth is dependent upon the adaptive immune system. We observe significantly increased numbers of antigen-specific CD8(+) T lymphocytes and CD8(+) T cells with an activated phenotype in the tumor microenvironment at thermoneutrality. At the same time there is a significant reduction in numbers of immunosuppressive MDSCs and regulatory T lymphocytes. Notably, in temperature preference studies, tumor-bearing mice select a higher ambient temperature than non-tumor-bearing mice, suggesting that tumor-bearing mice experience a greater degree of cold-stress. 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.
authors.affiliation: Department of Immunology, Department of Animal Resources, and Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kokolus
authors.forename: Maegan L
authors.initials: ML
authors.lastname: Capitano
authors.forename: Chen-Ting
authors.initials: CT
authors.lastname: Lee
authors.forename: Jason W-L
authors.initials: JW
authors.lastname: Eng
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Waight
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Hylander
authors.forename: Sandra
authors.initials: S
authors.lastname: Sexton
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Hong
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gordon
authors.forename: Scott I
authors.initials: SI
authors.lastname: Abrams
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Repasky
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001772:Blood Cell Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006799:Housing, Animal / Q000592:standards*; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D016014:Linear Models; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology*; D013312:Stress, Physiological / Q000276:immunology*; D013696:Temperature
keywords: metabolism; murine tumor models