Comparison of the Anti-Tumor Effects of Various Whole-Body Hyperthermia Protocols: Correlation with HSP 70 Expression and Composition of Splenic Lymphocytes

Abstract

Whole-body hyperthermia (WBH) has been used as an adjunct approach to radio-/chemotherapy for tumor therapy for many years. However, the molecular mechanism underlying the enhancement of tumor control is not clearly understood. It has been hypothesized that WBH might activate immune system by inducing the expression of heat shock proteins (HSPs), which are thought to facilitate the presentation of tumor-specific antigens. In the present work, we examined the effects of various thermal doses of WBH on tumor growth delay and HSP70 levels in tumors on C57BL/6 mice, as well as on splenic lymphocyte subpopulations. The maximal WBH effect (about 40% decrease in tumor weight) was achieved by a 2-hour WBH treatment everyday at 40.0°C. By using this treatment schedule, the populations of CD3⁺/CD4⁺ T cells and CD3⁺/CD8⁺ T cells increased by 4 and 3 times, respectively, at the end of WBH treatment period. When the length of day-by-day WBH treatment was longer than 2 hours or the frequency of WBH treatment was lower than once a day, the effect of tumor growth delay and the population of CD3⁺ T lymphocyte in spleen increase were discounted. On the other hand, the HSP70 levels in tumor nodules rose continuously as the WBH treating time increased, but the populations of NK cells in spleen did not change significantly. The results suggest that an increased CD3⁺ T lymphocyte population is closely related to the anti-tumor effect of WBH, which might be a useful marker for effectiveness of hyperthermia. However, neither the levels of HSP70 nor the NK cell populations in spleen appear to correlate to tumor control.

• WBH
• B16 melanoma model
• Thermal dose
• HSP70
• Lymphocytes