Hyperthermia May Stimulate Immune System

BUFFALO, NY--Whole body hy-perthermia, similar to that of a prolonged mild fever, results in antitumor effects that may be due to increased immune system activity and increased induction of heat shock proteins (HSPs). "These proteins are the primary protectors of cells against further heat exposure and other stresses," said John Subjeck, PhD, of Roswell Park Cancer Institute, at the first meeting of the Regional Cancer Center Consortium for Biological Therapy of Cancer, hosted by Roswell Park.

In murine studies, the Roswell Park researchers have determined that whole body hyperthermia can induce tumor cell apoptosis by simulating the thermal element of a mild fever. This tumor cell killing appears to be due, in large part, to the increased activity of natural killer cells. Dr. Subjeck also presented evidence that tumor vascular and cell adhesion proteins can be affected by this treatment.

"We were somewhat surprised to learn that heat shock proteins could be induced by very mild, low-temperature heat treatments extended for several hours," he said. Observing that this same mild hyperthermia treatment led to alterations in lymphocyte cytoskeleton, uropod formation, and protein kinase C activation and distribution, the researchers began to look more closely at various immune system functions. "We found that all of these biological properties and antitumor effects could be tempered by heat shock protein production," he noted.

Focus on Large Heat Shock Proteins

Current research at Roswell Park is focused on the large-molecular-weight families of HSPs, particularly HSP110 and GRP170, that protect cells from damage by heat, anoxia, and other stresses. HSP110, in particular, has the ability to recognize denatured proteins and help repair them, and probably does so more effectively than any of the other HSPs.

"We are quite excited about these large HSPs because almost nothing is known about their functions, while some of the smaller HSPs have been studied intensively," he noted. A trial is about to begin at Roswell Park that is similar to one underway at M.D. Anderson in the laboratory of Dr. Joan Bull. "We will test the effects of mild hyperthermia on the immune responses and HSP induction in patients with advanced cancer," Dr. Subjeck said. "In the near future, we plan to combine this treatment with other types of cancer immunotherapies."