Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

Abstract

There is increasing documentation of significant survival benefits achieved in cancer patients treated with hyperthermia in combination with radiation and/or chemotherapy. Most evidence collected regarding the mechanisms by which hyperthermia positively influences tumor control has centered on in vitro data showing the ability of heat shock temperatures (usually above 42 degrees C) to result in radio- or chemosensitization. However, these high temperatures are difficult to achieve in vivo, and new thermometry data in patients reveal that much of the tumor and surrounding region is only heated to 40-41 degrees C or less as a result of vascular drainage from the target zone of the heated tumor. Thus, there is now a growing appreciation of a role for mild hyperthermia in the stimulation of various arms of the immune system in contributing to long term protection from tumor growth. Indeed, a review of recent literature suggests the existence of an array of thermally sensitive functions which may exist naturally to help the organism to establish a new "set point" of immune responsiveness during fever. This review summarizes recent literature identifying complex effects of temperature on immune cells and potential cellular mechanisms by which increased temperature may enhance immune surveillance.

Short-Term Hyperthermia Promotes the Sensitivity of MCF-7 Human Breast Cancer Cells to Paclitaxel

“…2A, B). These findings may indicate that the anti-tumor activity caused by single hyperthermia was mainly due to activation of the immune system, 20) but not to a direct tumor-killing effect. In a previous study, the activation of both caspase-8 and 9 was found to mediate the enhancement of tumor necrosis factor (TNF)-induced apoptosis in MCF-7 cells.…”

Hyperthermia, Radiation and Chemotherapy: The Role of Heat in Multidisciplinary Cancer Care

“…The disadvantages are systemic stress and a limitation to <42°C due to thermosensitivity of critical tissues like heart, liver and brain. Thus the thermal goals of systemic therapy are usually more modest than local heating techniques, and intended for activation of drugs (48) or enhancement of immunologic response (49)(50)) rather than radiosensitization. When heating the whole body, normal body-cooling mechanisms such as respiration and skin cooling must be blocked by thermally insulating the patient and preheating the breathing circuit.…”

Studies on Certain Heat Induced Changes of Erythrocyte Membrane with Supplementation of Ascorbic Acid and Alteration of Dietary Protein Level

“…Mild elevation of temperature favours the cells to readjust the homeostatic equilibrium [5]. Fever appears to be an evolutionarily conserved response to bacterial or viral infection and may have survival benefits [6]. Again, when an individual is exposed to temperature above the zone of thermal neutrality, heat appears as a stress and changes occur in different physiological systems, such as cardiovascular, respiratory, endocrines, neural etc.…”