Study The Biologic Effect Of Alternate Thermal Treatments On Tumor

Malignant tumor is one of common diseases with the highest morbidity andmortality. However, the effect of major tumor treatments including surgery,radiotherapy and chemotherapy is still unsatisfactory, especially for metastatic tumor.Thermal modalities which include cryosurgery and hyperthermia destruct tumorthrough the external energy intervention. Compared with traditional therapy, thermalmodalities realize tumor treatment by changing the temperature of tumor tissue in ashort period with advantages of minimal invasion and lower side effects. However,the limitations of cryosurgery or hyperthermia alone greatly affect its clinicalapplication.A novel alternate cooling and heating thermal treatment system was developed inour laboratory. Based on the previous research, we studied the biologic effect andmechanism of alternate cooling and heating treatments on tumor in this study. Thealternate treatment including cryosurgery (cooling at-20℃for5min), thawing,followed by hyperthermia (heating at50℃for10min), was locally applied to4T1murine mammary carcinoma in3weeks after implantation. After treatment, tumormicrovasculature damage was observed through advanced vascular imagingtechnology in3D level. The apoptosis and necrosis of tumor tissue,immunostimulatory molecules, immunosuppressive cells and lymphocytes infiltrationwere studied in tumor microenvironment using pathologic analysis. Furtherinvestigations were performed to study the whole body anti-tumor response to thetreatment, including the dynamic changes of MDSC in peripheral blood using flowcytometry and immune cells (MDSC, TAM, DC,CD8+T cell) in spleen usingimmunofluorescence staining. The control groups included tumor-bearing controlgroup, resection group, cryosurgery (cooling at-20℃for15min) group andhyperthermia (heating at50℃for15min) group.The results were showed the alternate treatment caused the most damage to tumormicrovasculature and tumor tissue. HSP70and HMGB1were released,immunosuppression cells significantly reduced and much more pronouncedlymphocytes infiltration found after the alternate treatment. Comparing to hyperthermia and cryosurgery, anti-tumor immune response was initiated in primarytumor. Moreover, MDSC in peripheral blood and spleen significantly reduced, at thesame time, the number of DC and CD8+T in spleen increased, which indicated that thewhole body anti-tumor response was stimulated by the treatment. The alternatethermal treatment not only cures primary tumors, but also inhibits the secondarytumor growth. Thus the alternate treatment might be further developed as a noveltherapeutic strategy against metastatic tumor.