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Frontiers of Medicine

Front. Med.    2014, Vol. 8 Issue (1) : 1-5     DOI: 10.1007/s11684-014-0309-3
Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected skin diseases
Xinghua Gao(), Hongduo Chen
Department of Dermatology, the First Hospital of China Medical University, Shenyang 110001, China
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Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39β°C to 40β°C) can modulate the activities of immune cells, including antigen-presenting cells, T cells, and natural killer cells. Heat shock temperature (41β°C to 43β°C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (>43β°C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.

Keywords hyperthermia      HPV      immune response      virus      tumor     
Corresponding Authors: Gao Xinghua,   
Issue Date: 26 April 2014
 Cite this article:   
Xinghua Gao,Hongduo Chen. Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected skin diseases[J]. Front. Med., 2014, 8(1): 1-5.
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Articles by authors
Xinghua Gao
Hongduo Chen
HSPHSP receptor(s)
gp96CD91, TLR-2, TLR-4, SR-A
HSP60CD14, TLR-4, TLR-2
HSP70CD14, CD40, CD91, Lox-1,TLR-2, TLR-4
CalreticulinCD91, SR-A
Tab.1  Characterized HSPs and associated receptors (adopted and revised from Ref.β[-])
Fever-range (39β°C to 40β°C) and heat shock (41β°C to 43β°C) temperatureIncreases antigen uptake and phagocytosis by DCs and macrophagesStimulates antigen processing by increasing the expression of immunoproteasome, lmp2, and lmp7Augments cross-presentation in DCs and primes naive CD8+ T cells to form CTLsInduces DC activation and maturationEnhances the migration of DCs to draining lymph nodesIncreases the expression of TLR4Upregulates the expression of MHC class II, CD80, CD86, and CD40 in DCsPromotes lymphocyte trafficking to lymphoid and tumor tissueRegulates lymphocyte survival and persistence in peripheral tissue by inducing c-FLIP degradationEnhances the effector T cell function: increased expression of CD95L in CTLs and augment NK cell migration and lysisIncreases class I MHC expression on tumor cell surfaceUpregulates the expression of tumor antigensInduces expression of HSPs that provide “danger signal” for DC activationEnhances the susceptibility of tumor cells to CTL-mediated lysis
Cytotoxic temperature (>43β°C)Creates an antigen source to induce an anti-tumor immune response
Tab.2  Immunomodulating effects of hyperthermia (adopted and revised from Ref. [])
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