Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature

被引:256
作者
Kokolus, Kathleen M. [1 ]
Capitano, Maegan L. [1 ]
Lee, Chen-Ting [1 ]
Eng, Jason W. -L. [1 ]
Waight, Jeremy D. [1 ]
Hylander, Bonnie L. [1 ]
Sexton, Sandra [2 ]
Hong, Chi-Chen [3 ]
Gordon, Christopher J. [4 ]
Abrams, Scott I. [1 ]
Repasky, Elizabeth A. [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA
[2] Roswell Pk Canc Inst, Dept Anim Resources, Buffalo, NY 14263 USA
[3] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA
[4] US EPA, Tox Assessment Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27709 USA
关键词
murine tumor models; metabolism; BROWN ADIPOSE-TISSUE; TRADE-OFFS; CANCER; MOUSE; MODELS; THERMONEUTRALITY; STRESS; CELLS; COLD; INTERLEUKIN-2;
D O I
10.1073/pnas.1304291110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 degrees 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 degrees 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.
引用
收藏
页码:20176 / 20181
页数:6
相关论文
共 39 条
[1]   Brown adipose tissue: Function and physiological significance [J].
Cannon, B ;
Nedergaard, J .
PHYSIOLOGICAL REVIEWS, 2004, 84 (01) :277-359
[2]   Yes, even human brown fat is on fire! [J].
Cannon, Barbara ;
Nedergaard, Jan .
JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (02) :486-489
[3]   Origins of tumor-associated macrophages and neutrophils [J].
Cortez-Retamozo, Virna ;
Etzrodt, Martin ;
Newton, Andita ;
Rauch, Philipp J. ;
Chudnovskiy, Aleksey ;
Berger, Cedric ;
Ryan, Russell J. H. ;
Iwamoto, Yoshiko ;
Marinelli, Brett ;
Gorbatov, Rostic ;
Forghani, Reza ;
Novobrantseva, Tatiana I. ;
Koteliansky, Victor ;
Figueiredo, Jose-Luiz ;
Chen, John W. ;
Anderson, Daniel G. ;
Nahrendorf, Matthias ;
Swirski, Filip K. ;
Weissleder, Ralph ;
Pittet, Mikael J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (07) :2491-2496
[4]   HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment [J].
Corzo, Cesar A. ;
Condamine, Thomas ;
Lu, Lily ;
Cotter, Matthew J. ;
Youn, Je-In ;
Cheng, Pingyan ;
Cho, Hyun-Il ;
Celis, Esteban ;
Quiceno, David G. ;
Padhya, Tapan ;
McCaffrey, Thomas V. ;
McCaffrey, Judith C. ;
Gabrilovich, Dmitry I. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (11) :2439-2453
[5]   Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease [J].
Danna, EA ;
Sinha, P ;
Gilbert, M ;
Clements, VK ;
Pulaski, BA ;
Ostrand-Rosenberg, S .
CANCER RESEARCH, 2004, 64 (06) :2205-2211
[6]   UCP1 Ablation Induces Obesity and Abolishes Diet-induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality [J].
Feldmann, Helena M. ;
Golozoubova, Valeria ;
Cannon, Barbara ;
Nedergaard, Jan .
CELL METABOLISM, 2009, 9 (02) :203-209
[7]   IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells [J].
Fisher, Daniel T. ;
Chen, Qing ;
Skitzki, Joseph J. ;
Muhitch, Jason B. ;
Zhou, Lei ;
Appenheimer, Michelle M. ;
Vardam, Trupti D. ;
Weis, Emily L. ;
Passanese, Jessica ;
Wang, Wan-Chao ;
Gollnick, Sandra O. ;
Dewhirst, Mark W. ;
Rose-John, Stefan ;
Repasky, Elizabeth A. ;
Baumann, Heinz ;
Evans, Sharon S. .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (10) :3846-3859
[8]   Fuel feeds function: Energy metabolism and the T-cell response [J].
Fox, CJ ;
Hammerman, PS ;
Thompson, CB .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (11) :844-852
[9]   RESULTS OF TREATMENT OF 255 PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA WHO RECEIVED HIGH-DOSE RECOMBINANT INTERLEUKIN-2 THERAPY [J].
FYFE, G ;
FISHER, RI ;
ROSENBERG, SA ;
SZNOL, M ;
PARKINSON, DR ;
LOUIE, AC .
JOURNAL OF CLINICAL ONCOLOGY, 1995, 13 (03) :688-696
[10]   Heat or Insulation: Behavioral Titration of Mouse Preference for Warmth or Access to a Nest [J].
Gaskill, Brianna N. ;
Gordon, Christopher J. ;
Pajor, Edmond A. ;
Lucas, Jeffrey R. ;
Davis, Jerry K. ;
Garner, Joseph P. .
PLOS ONE, 2012, 7 (03)