Local tumour hyperthermia as immunotherapy for metastatic cancer - PubMed (original) (raw)

Review

Local tumour hyperthermia as immunotherapy for metastatic cancer

Seiko Toraya-Brown et al. Int J Hyperthermia. 2014 Dec.

Abstract

Abstract Local tumour hyperthermia for cancer treatment is currently used either for ablation purposes as an alternative to surgery or less frequently, in combination with chemotherapy and/or radiation therapy to enhance the effects of those traditional therapies. As it has become apparent that activating the immune system is crucial to successfully treat metastatic cancer, the potential of boosting anti-tumour immunity by heating tumours has become a growing area of cancer research. After reviewing the history of hyperthermia therapy for cancer and introducing methods for inducing local hyperthermia, this review describes different mechanisms by which heating tumours can elicit anti-tumour immune responses, including tumour cell damage, tumour surface molecule changes, heat shock proteins, exosomes, direct effects on immune cells, and changes in the tumour vasculature. We then go over in vivo studies that provide promising results showing that local hyperthermia therapy indeed activates various systemic anti-tumour immune responses that slow growth of untreated tumours. Finally, future research questions that will help bring the use of local hyperthermia as systemic immunotherapy closer to clinical application are discussed.

Keywords: Biology; immunotherapy; local hyperthermia; tumor immunology; tumor immunotherapy.

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Figures

Figure 1.

Figure 1.

Different mechanisms of immune activation induced by locally heating tumours. (A) Heated tumour cells increase the surface expression of MICA, a NKG2D ligand, and MHC class I, making the tumour cells more sensitive to lysis by NK cells and CD8+ T cells, respectively. (B) Heated tumour cells release HSPs, which activate NK cells and APCs. HSPs contain potential tumour antigens, and APCs take up the HSP-antigen complex and cross present the antigen to CD8+ T cells. (C) Heated tumour cells release exosomes. Exosomes also contain potential tumour antigens, and APCs take up the antigen and cross present the antigen to CD8+ T cells. (D) Immune cells, such as NK cells, CD8+ T cells and DCs, in the tumour also get heated and become activated. (E) The tumour vasculature becomes more permeable and may have increased adhesion molecule expression after heating, which may facilitate better trafficking of immune cells between the tumour and dLN.

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