The cryo-thermal therapy eradicated melanoma in mice by eliciting CD4+T-cell-mediated antitumor memory immune response.
Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used. The cryo-thermal therapy induced regression of implanted melanoma and prolonged long-term survival while inhibiting lung metastasis. It also promoted the activation of CD4+CD25-conventional T cells, while reduced the percentage of CD4+CD25+regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the spleen, lung and blood. Furthermore, the cryo-thermal therapy enhanced the cytolytic function of CD8+T cells and induced differentiation of CD8+T cells into memory stem T cell (TSCM), and differentiation of CD4+T cells into dominant CD4-CTL, Th1 and Tfh subsets in the spleen for 90 days after the treatment. It was found that good therapeutic effect was mainly dependent on CD4+T cells providing a durable memory antitumor immune response. At the same time, significant increase of serum IFN-γ was also observed to provide an ideal microenvironment of antitumor immunity. Further study showed that the rejection of re-challenge of B16F10 but not GL261 tumor in the treated mice in 45 or 60 days after the treatment, implied a strong systemic and melanoma-specific memory antitumor immunity induced by the treatment. Thus the cryo-thermal therapy would be considered as a new therapeutic strategy to prevent tumor recurrence and metastasis with potential clinical applications in the near future.
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Kun
K
He
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Ping
P
Liu
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Lisa X
LX
Xu
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D053645:Interleukin-2 Receptor alpha Subunit