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      Water-filtered Infrared A (wIRA) Irradiation : From Research to Clinical Settings 

      Whole-Body Hyperthermia (WBH): Historical Aspects, Current Use, and Future Perspectives

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      Springer International Publishing

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          Abstract

          Whole-body hyperthermia (WBH), induced by passive heating, and active fever therapy induced by pyrogenic drugs, have been accepted as therapy of various diseases for many decades. However, the introduction of antibiotics and anti-inflammatory drugs caused the interest in this traditional therapy to decline. The development of modern WBH using infrared irradiation (IR) started in the 1960s.

          Three levels of hyperthermia differ fundamentally in practical implementation, mechanisms of action, and indications. Mild WBH is stress-free and aims mainly to muscle relaxation and increased perfusion in the locomotor system. Fever-range whole-body hyperthermia (FRWBH) requires a more extensive nursing care due to major thermoregulatory stress. FRWBH is applied for stimulation of anti-tumor immune responses and for anti-inflammatory effects in case of chronic inflammation. Moreover, anti-depressive effects of FRWBH could recently be shown. Extreme WBH needs an intensive care environment and aims to the direct damage of cancer cells or therapy-resistant pathogens. In general, inconsistent effects of WBH on blood perfusion must be taken into account if combined with medication.

          Two commercially available medical WBH devices both use water-filtered infrared-A (wIRA), but deviate in the practical implementation. Contraindications and the risk of side effects differ essentially between the three levels and must carefully be observed.

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          Fever and the thermal regulation of immunity: the immune system feels the heat.

          Fever is a cardinal response to infection that has been conserved in warm-blooded and cold-blooded vertebrates for more than 600 million years of evolution. The fever response is executed by integrated physiological and neuronal circuitry and confers a survival benefit during infection. In this Review, we discuss our current understanding of how the inflammatory cues delivered by the thermal element of fever stimulate innate and adaptive immune responses. We further highlight the unexpected multiplicity of roles of the pyrogenic cytokine interleukin-6 (IL-6), both during fever induction and during the mobilization of lymphocytes to the lymphoid organs that are the staging ground for immune defence. We also discuss the emerging evidence suggesting that the adrenergic signalling pathways associated with thermogenesis shape immune cell function.
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            The Intriguing History of Cancer Immunotherapy

            Immunotherapy is often perceived as a relatively recent advance. In reality, however, one should be looking for the beginnings of cancer immunotherapy under different names as far as in the Antiquity. The first scientific attempts to modulate patients' immune systems to cure cancer can be attributed to two German physicians, Fehleisen and Busch, who independently noticed significant tumor regression after erysipelas infection. The next significant advances came from William Bradley Coley who is known today as the Father of Immunotherapy. It was Coley who first attempted to harness the immune system for treating bone cancer in 1891. His achievements were largely unnoticed for over fifty years, and several seminal discoveries in the field of Immunology, such as the existence of T cells and their crucial role in immunity in 1967, stepped up the research toward cancer immunotherapy known today. The following paper tracks cancer immunotherapy from its known beginnings up until recent events, including the 2018 Nobel Prize award to James Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as potential therapeutic targets. That work has led to the successful development of new checkpoint inhibitors, CAR T-cells and oncolytic viruses and the pace of such advances brings the highest hope for the future of cancer treatment.
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              Temperature matters! And why it should matter to tumor immunologists.

              A major goal of cancer immunology is to stimulate the generation of long-lasting, tumor antigen-specific immune responses that recognize and destroy tumor cells. This article discusses advances in thermal medicine with the potential to improve cancer immunotherapy. Accumulating evidence indicates that survival benefits are accorded to individuals who achieve an increase in body temperature (i.e. fever) following infection. Furthermore, accumulating evidence indicates that physiological responses to hyperthermia impact the tumor microenvironment through temperature-sensitive check-points that regulate tumor vascular perfusion, lymphocyte trafficking, inflammatory cytokine expression, tumor metabolism, and innate and adaptive immune function. Nevertheless, the influence of thermal stimuli on the immune system, particularly the antitum or immune response, remains incompletely understood. In fact, temperature is still rarely considered as a critical variable in experimental immunology. We suggest that more attention should be directed to the role of temperature in the regulation of the immune response and that thermal therapy should be tested in conjunction with immunotherapy as a multi-functional adjuvant that modulates the dynamics of the tumor microenvironment.
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                Author and book information

                Book Chapter
                2022
                May 06 2022
                : 143-154
                10.1007/978-3-030-92880-3_11
                f604c7bb-5e2a-460b-ae9f-8d7386f0509b
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