Bonnie L Hylander

Christopher J Gordon

Elizabeth A Repasky

Jason W Eng

Kathleen M Kokolus

Maegan L Capitano

Scott I Abrams

Journal for ImmunoTherapy of Cancer

English

PubMed

Crossref

POSTER PRESENTATION Open AccessThe impact of metabolic stress on anti-tumorimmunity in laboratory miceKathleen M Kokolus1*, Maegan L Capitano1, Jason W Eng1, Bonnie L Hylander1, Christopher J Gordon2,Scott I Abrams1, Elizabeth A Repasky1From Society for Immunotherapy of Cancer 28th Annual MeetingNational Harbor, MD, USA. 8-10 November 2013There is an underappreciated amount of physiologicalstress placed on laboratory mice including that dueto standard, required housing at sub-thermoneutraltemperature. This condition results in an increase inmetabolism needed to produce heat necessary to maintainbody temperature. Since body temperature maintenanceis a high priority for survival, we hypothesized that meta-bolic energy may be allocated to body temperature main-tenance at the expense of the anti-tumor immuneresponse under standard cool housing temperatures.At ambient temperatures of 30-31°C, which is consideredthe thermoneutral temperature (TT) for mice, restingmetabolic rate is sufficient to generate enough heat tomaintain body temperature. However, mice are kept at acooler standard temperature (ST; 21-23°C). Our datareveals increased heat-seeking behavior in tumor-bearingmice housed at ST indicating a physiological drive foradditional ambient warmth, likely needed to lessen theenergetic burden of maintaining body temperature. Wefound significantly delayed tumor growth rates and areduction in metastasis in mice housed at TT comparedto those at ST. We investigated immunodeficient miceand mice depleted for CD8+ T cells and found no differ-ences in tumor growth between mice housed at ST andTT suggesting a role for the T cell dependent immuneresponse. Because the activation of CD8+ T cells is anenergetically demanding process we predicted the functionof these cells would be diminished in animals at STsince more metabolic resources may be diverted toheat production. According to this hypothesis we saw anincrease in glucose uptake in the lymph nodes of tumor-bearing mice as well as an increase in Glut-1 expressionon splenic CD8+ T cells in mice maintained at TTsuggesting increased metabolic activity in these cellpopulations. Our studies also revealed more antigenspecific CD8+ T cells within the lymph node and tumormicroenvironment of animals housed at TT compared tothose housed at ST. Finally, our data has also shown asignificantly increased number of immunosuppressive cellsubsets including Gr-1+CD11b+ myeloid derived suppres-sor cells and Foxp3+ cells in mice maintained at ST com-pared to those at TT. These data demonstrate that tumorgrowth and anti-tumor immune control in laboratorymice is highly influenced by cold stress. We hypothesizethat the amount of energy available to T cells understandard cool housing conditions is reduced. Sincemetabolism and its role in T cell activation is increasinglymodeled in laboratory mice, it is essential to take intoaccount the impact that housing temperature has on anti-tumor immune activity.Authors’ details1Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.2US Environmental Protection Agency, Research Triangle, NC, USA.Published: 7 November 2013doi:10.1186/2051-1426-1-S1-P122Cite this article as: Kokolus et al.: The impact of metabolic stress onanti-tumor immunity in laboratory mice. Journal for ImmunoTherapy ofCancer 2013 1(Suppl 1):P122.1Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USAFull list of author information is available at the end of the articleKokolus et al. Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P122http://www.immunotherapyofcancer.org/content/1/S1/P122© 2013 Kokolus et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited. on November 8, 2020 by guest. Protected by copyright.http://jitc.bmj.com/J Immunother Cancer: first published as 10.1186/2051-1426-1-S1-P122 on 7 November 2013. Downloaded from 

The impact of metabolic stress on anti-tumor immunity in laboratory mice

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The impact of metabolic stress on anti-tumor immunity in laboratory mice

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