Document Detail

Effector CD8+ T cell IFN-γ production and cytotoxicity are enhanced by mild hyperthermia.
MedLine Citation:
PMID:  22235780     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Clinical trials combining hyperthermia with radiation and/or chemotherapy for cancer treatment have resulted in improved overall survival and control of local recurrences. The contribution of thermally enhanced anti-immune function in these effects is of considerable interest, but not understood; studies on the fundamental effects of elevated temperature on immune effector cells are needed. The goal of this study is to investigate the potential of mild hyperthermia to impact tumour antigen-specific (Ag) effector CD8+ T cell functions.
METHOD: Pmel-1 Ag-specific CD8+ T cells were exposed to mild hyperthermia and tested for changes in IFN-γ production and cytotoxicity. Additionally, overall plasma membrane organisation and the phosphorylation of signalling proteins were also investigated following heat treatment.
RESULTS: Exposing effector Pmel-1-specific CD8+ T cells to mild hyperthermia (39.5°C) resulted in significantly enhanced Ag-specific IFN-γ production and tumour target cell killing compared to that seen using lower temperatures (33° and 37°C). Further, inhibition of protein synthesis during hyperthermia did not reduce subsequent Ag-induced IFN-γ production by CD8+ T cells. Correlated with these effects, we observed a distinct clustering of GM1(+) lipid microdomains at the plasma membrane and enhanced phosphorylation of LAT and PKCθ which may be related to an observed enhancement of Ag-specific effector CD8+ T cell IFN-γ gene transcription following mild hyperthermia. However, mitogen-mediated production of IFN-γ, which bypasses T cell receptor activation with antigen, was not enhanced.
CONCLUSIONS: Antigen-dependent effector T cell activity is enhanced following mild hyperthermia. These effects could potentially occur in patients being treated with thermal therapies. These data also provide support for the use of thermal therapy as an adjuvant for immunotherapies to improve CD8+ effector cell function.
Thomas A Mace; Lingwen Zhong; Kathleen M Kokolus; Elizabeth A Repasky
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group     Volume:  28     ISSN:  1464-5157     ISO Abbreviation:  Int J Hyperthermia     Publication Date:  2012  
Date Detail:
Created Date:  2012-01-12     Completed Date:  2012-05-08     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  8508395     Medline TA:  Int J Hyperthermia     Country:  England    
Other Details:
Languages:  eng     Pagination:  9-18     Citation Subset:  IM    
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MeSH Terms
CD8-Positive T-Lymphocytes / immunology*
Cell Line, Tumor
Cell Survival
Hot Temperature*
Interferon-gamma / immunology*
Melanoma-Specific Antigens / immunology*
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Antigen, T-Cell, alpha-beta / genetics
Spleen / cytology
Grant Support
2 T32 CA085183/CA/NCI NIH HHS; CA16056/CA/NCI NIH HHS; P30 CA016056/CA/NCI NIH HHS; P30 CA016056-33S4/CA/NCI NIH HHS; R01 CA071599/CA/NCI NIH HHS; R01 CA071599-11/CA/NCI NIH HHS; R01 CA071599-11/CA/NCI NIH HHS; R01 CA135368/CA/NCI NIH HHS; R01 CA135368-01A1/CA/NCI NIH HHS; R01 CA135368-01A1/CA/NCI NIH HHS; T32 CA085183/CA/NCI NIH HHS; T32 CA085183-07/CA/NCI NIH HHS
Reg. No./Substance:
0/Melanoma-Specific Antigens; 0/Receptors, Antigen, T-Cell, alpha-beta; 82115-62-6/Interferon-gamma

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