Annette Dieing, Olaf Ahlers, Bert Hildebrandt, Thoralf Kerner, Ingo Tamm, Kurt Possinger and Peter Wust
Department of Oncology and Hematology, Charite ́ Campus Mitte, University Medicine Berlin, Germany, Schumannstrasse 20/21, D-10117 Berlin, Germany. Department of Anesthesiology and Intensive Care Medicine, Charite ́ Medical School, University Medicine Berlin, Campus Virchow Clinic, D-13353 Berlin, Germany. Medical Clinic, Department of Hematology and Oncology, Charite ́ Medical School, University Medicine Berlin, Campus Virchow Clinic, D-13353 Berlin, Germany. Department of Radiation Medicine, Charite ́ Medical School, University Medicine Berlin, Campus Virchow Clinic, D-13353 Berlin, Germany.
Therapeutical hyperthermia has been considered for cancer therapy since William Coley observed tumor remission after induction of fever by bacterial toxins at the end of the 19th century. Because fever is associated with a variety of immunological reactions, it has been suspected, that therapeutical hyperthermia might also activate the immune system in a reproducible manner and thereby positively influence the course of the disease. During the last decade, new insight has been gained regarding the immunological changes taking place during therapeutic hyperthermia. In this chapter, we review the most relevant data known about the effect of hyperthermia on the immune system with special focus on alterations induced by therapeutical whole-body hyperthermia (WBH) in cancer patients.
The medical subject headings (MeSH) database introduced the term ‘‘hyperthermia induced’’ in 1984 and defined it as ‘‘abnormally high temperature intentionally induced in living things regionally or whole body. It is most often induced by radiation (heat waves, infra-red), ultrasound or drugs’’ (http://www.ncbi.nlm.nih.gov). This definition implies that hyperthermia is a condition provoked by an external source and thus is clearly to be discriminated from other causes of elevated body temperatures, such as fever, malignant hyperthermia or other forms of heat injury like heat stroke. Regarding hyperthermia in this narrower sense, most scientific findings on the effect of external heat application on living organisms have been generated in the scope of cancer research, where preclinical and clinical approaches have been investigated for more than half a decade (reviewed in Hildebrandt et al., 2002; Wust et al., 2002; van der Zee, 2002). Pioneering radiobiological studies established a synergism between temperature elevation and radiation in the early 1970s (Dewey, 1994). The clinical relevance of these findings has been proven in a number of randomized clinical studies on locoregional hyperthermia, with super-agonistic effects observed for the combination of hyperthermia and certain cytotoxic drugs (Wust et al., 2002; van der Zee, 2002). In addition, a number of phase II studies suggest a beneficial effect for whole-body hyperthermia (WBH) as an adjunct to chemotherapy (Hildebrandt et al., 2005). But even if it appears to be proven that local and regional radiofrequency hyperthermia approaches are suitable to enhance the effect of radiotherapy and chemotherapy in a variety of human malignancies, most of the underlying mechanisms are still poorly understood.