Abstract 790: Are laboratory mice too cold to mount effective anti-tumor immune responses

Abstract

Abstract During the course of experiments to determine the effects of elevated body temperature on anti-tumor immune responses, we unexpectedly observed that in control animals bearing tumors and maintained under standard room temperatures (IACUC-compliant, 21-23°C), the core temperature actually began to fall significantly as the tumors grew larger. Moreover, using thermal preference analyses, we found that animals bearing tumors exhibit considerable heat-seeking behavior. In an attempt to keep body temperature within the normal range (∼37°C), we began to house tumor bearing mice in a warmer environment (i.e., 28-30°C) considered to be the thermoneutral temperature for mice, as apposed to IACUC compliant temperatures which are considered mildly hypothermic for mice. Decisions that have resulted in the mildly cooler environmental temperature required in animal colonies have been generally based upon optimizing air-handling capacity of fumes and the thermal comfort of personnel rather than the optimal thermal comfort of animals (hence the requirements for multiple mice per cage to allow for huddling). When we analyzed tumor growth under thermoneutral conditions, syngeneic tumor growth was significantly delayed in animals maintained at 28-30°C compared to tumor growth in animals maintained at 21-23 oC. If the same comparison is made using SCID mice, no difference in tumor growth rate is observed. More specifically, BALB/c, C57BL/6 and SCID mice were housed in either standard room temperature (RT = 21-23°C) or in a warmer ambient temperature (WR = 28-30°C). Mice were then implanted with a syngeneic tumor (CT26 for BALB/c and SCID; B16.F10 for C57BL/6) subcutaneously and tumor growth was monitored. Tumor growth in C57BL/6 and BALB/c mice was inhibited when mice were housed in the warmer ambient temperature compared to animals maintained in standard room temperature. There was no difference in CT26 tumor growth in SCID mice. This finding suggested that the T cell-dependent anti-tumor immune response may be at least partly responsible for enhanced tumor growth control under conditions of warmer ambient temperature. Results of depletion studies in C57BL/6 mice bearing B16.F10 tumors, showed that both CD4+ and CD8+ T cells were required for inhibition of tumor growth in the warmer ambient temperature. In BALB/c mice bearing CT26 tumors, only CD8+ T cells were required to inhibit tumor growth. These findings suggest that the natural anti-tumor immune response exhibited by mice housed in standard colony conditions is sub-optimal and can be improved simply by housing mice under thermoneutral conditions. T cell dependent anti-tumor immunity appears to be at least one immune mechanism which is improved when animals are not cold stressed. Supported by NIH R01 CA 135368. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 790. doi:10.1158/1538-7445.AM2011-790