Temperature response: New concepts in telethermometry offer theories about tumor evasion mechanisms

Key Points

Curitiba, Brazil - Research undertaken to evaluate the intensity of inflammation induced using imiquimod 5 percent cream (Aldara, Graceway Pharmaceuticals) for the treatment of basal cell carcinoma (BCC) has provided interesting insight not only into the potential role of local skin temperature as a marker of the therapeutic response to the topical immune response modifier, but also as a mechanism by which the tumor may evade the host immune system, says J. Hermenio C. Lima, M.D., D.Sc.

Telethermometry

In research conducted at the Federal University of Paraná, Curitiba, Brazil, Dr. Lima and colleagues used dynamic area telethermometry to measure skin temperature kinetics to thermal challenge stimulation before and after 15 days of imiquimod treatment in patients with BCC. This technology measures skin temperature with precision to 0.1 degree Celsius, and so would allow detection of relatively small variations in temperature associated with imiquimod-induced inflammation and increased blood flow.

"It is well known that the efficacy of imiquimod in treating BCC seems to correlate with the magnitude of the inflammatory reaction it induces, and so we undertook this study to see if we could use skin temperature to predict efficacy by measuring the inflammatory response. Our experience establishes the feasibility of this approach and revealed there are interpatient differences in temperature kinetics," says Dr. Lima, associate professor of clinical immunology and allergy, Federal University of Paraná, and currently completing a research fellowship in the department of dermatology, Clinical Unit for Research Trials in Skin, Massachusetts General Hospital, Harvard Medical School, Boston.

"The incidental finding of a lower temperature of the untreated BCC was a surprise, considering that vascular proliferation is a feature of these tumors. We believe we are the first to report this observation and are theorizing it may aid in tumor immune system evasion by acting to suppress T-lymphocyte activity."

Dr. Lima believes that the lower temperature of the BCCs may be explained by the superficial nature of the vessels. The capillaries supplying the tumor are so close to the skin surface that they may result in loss of heat to the external environment.

Postulating that a treatment-induced increase in tumor temperature plays an essential role in enabling the host immune system to destroy the tumor cells, the researchers are now testing this concept in a clinical trial investigating whether the response to topical imiquimod or other therapies (5-fluorouracil) may be enhanced by using strategies to increase tumor temperature. Their hope is that this combination approach will improve the efficacy rate of the topical therapy and also hasten the response so that the duration of treatment may be shortened.

"All of the BCCs treated in our study cleared with topical imiquimod, but there was variation in the speed of the response. We noticed that an increase in temperature preceded the onset of a visible inflammatory response, and we think this information might be useful in predicting patients who are likely to respond quicker and may be able to use imiquimod for a shorter duration," Dr. Lima says.

Disclosure: Dr. Lima has previously been a speaker for Intendis, which marketed Aldara in Brazil. He received no financial support for the research he presented.