Abstract 4739: Effects of whole-body heat treatment on antigen specific T cells responses.
Authors: Kobayashi Yasunobu , Ito Yusuke , Ostapenko Valentina V. , Sakai Mayuko , Matsushita Norimasa , Imai Kenichiro , Shimizu Koichi , Aruga Atsushi , Tanigawa Keishi 
Published: August 2014

Abstract
Studies in mice showed that heat treatment in fever-range (approx. 38.5-40.5 deg C) stimulates a variety of T cells functions in vitro, ex vivo and in vivo. We previously introduced the heckel HT3000; an infrared A-irradiation device specifically designed for whole-body hyperthermia, and we are now studying how to combine it with cancer immuno-cell therapy such as adoptive transfer of activated T cells and autologous monocyte-derived dendritic cells (DCs)-based vaccination. In this study, using healthy volunteers, we examined the effects of fever-range whole body heat treatment on the function of peripheral T cells, and in particular their cytokines productions in response to various stimuli.
Volunteers were exposed to infrared A until the rectal temperature reached at 38.5 deg C. They were then wrapped in synthetic leather tent for 60 min in order to maintain the core body temperature in fever-range. Peripheral blood was obtained four times; prior to the treatment, immediately after the treatment, 24 h after the treatment, and 48 h after the treatment. PBMC were then prepared and co-cultured with antigen-loading autologous DCs for 24 h in order to induce antigen specific cytokine productions in T cells.
We first examined IFNγ production in T cells in response to MHC class I restricted epitope peptides of CMV, EBV and Flu. When PBMCs were co-cultured with these peptides-labeled DCs, a marked increase in IFNγ production was observed in PBMCs prepared immediately after and 24 h after the heat treatment. Production of IFNγ in PBMCs prepared 48 h after the heat treatment returned to approximately the same level as in those without the treatment. These results indicate that heat treatment stimulates viral antigens-specific T cell responses, and its effect lasted for at least 24 h even after the heat treatment. Similarly, enhanced production of IFNγ in response to the tuberculin purified protein derivative was also observed immediately after and 24 h after the heat treatment. Compared with the responses to these recall antigens, non-recall antigen; KLH did not induce IFNγ production from PBMCs at any time popint of preparation. On the other hand, PMA/ionomycin-induced IFNγ production in PBMCs did not change during any time point of preparation.
Taken together, whole-body heat treatment in fever-range appeared to make profound impact on antigen-specific T cell responses, and could be a possible combination therapy to enhance the efficacy of cancer immuno cell therapy, such as adoptive transfer of activated T cells and DCs-based vaccination.
Citation Format: Yasunobu Kobayashi, Yusuke Ito, Valentina V. Ostapenko, Mayuko Sakai, Norimasa Matsushita, Kenichiro Imai, Koichi Shimizu, Atsushi Aruga, Keishi Tanigawa. Effects of whole-body heat treatment on antigen specific T cells responses. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4739. doi:10.1158/1538-7445.AM2013-4739