Immunologic response induced by synergistic effect of alternating cooling and heating of breast cancer

Abstract

In this study, the therapeutic effect and the induced anti-tumor immunity through the alternating cooling and heating was investigated using 4T1 murine mammary carcinoma, a common model of human metastatic breast cancer. While fifteen of seventeen regular mice were cured, primary recurrence and metastasis caused death of all the nude mice within one month after the same treatment. Histological analyses showed that viable cells existed in the tumor debris after the treatment, indicating that the direct killing effect was not the only therapeutic mechanism. Further investigation found rejection of tumor upon re-challenge, and anti-tumor immune response was studied. Stronger cytotoxicity T-lymphocyte (CTL) and Th1 cytokines response as well as infiltration of immunocytes were observed in the treated mice in comparison to those after the surgical resection. The results showed that the alternating cooling and heat could stimulate anti-tumor immunologic response in vivo and the underlying mechanisms will be further investigated in the near future.

Interleukin-6 Induced “Acute” Phenotypic Microenvironment Promotes Th1 Anti-Tumor Immunity in Cryo-Thermal Therapy Revealed By Shotgun and Parallel Reaction Monitoring Proteomics

“…In the past,, we indicated that cryo-thermal therapy increased the damage region of tumor, and led to severe destruction of tumor blood vessels 8 , 16 . Furthermore, we observed an increased local induction of Th1 type cytokines and recruitment of CD4 + and CD8 + T lymphocytes 10 , 17 , while the accumulation of immunosuppressive lymphocytes were drastically reduced 10 , 18 . However, cryo-thermal therapy appears to induce more systematic and profound responses in vivo , which therefore appeals for a comprehensive and system-wide analysis towards better understanding the anti-tumor mechanism at a molecular level.…”

The cryo-thermal therapy-induced IL-6-rich acute pro-inflammatory response promoted DCs phenotypic maturation as the prerequisite to CD4+T cell differentiation

“…In our previous study, a novel tumour therapeutic modality was developed for cryo-thermal therapy by alternating liquid nitrogen (LN2) cooling and radio frequency (RF) heating of tumour tissues [22][23][24][25][26][27]. Using a highly malignant murine 4T1 breast cancer xenograft model, we found that cryo-thermal therapy remodelled the tumour microenvironment from chronic inflammatory to an acute phenotype.…”

Study of Tumor Growth under Hyperthermia Condition

“…In fact, during the treatment, both the temperature gradient and inhomogeneity existed, and the higher temperature could impair tumor cells by denaturation or destruction of cellular membrane, cellular skeleton, and nucleus [48]. The long-term mild hyperthermia treatment might also affect the activities of enzymes in different pathways associated with tumor cell metabolism and proliferation, stimulate the immunology factors such as hsp70, which could arouse body system defense and eliminate tumor cells specifically [49]. Besides, Song's study [50] revealed that under mild hyperthermia (41~42°C, 30 min) blood perfusion in tumor tissue could increase 1.5~2 folds as compared to that prior to the treatment.…”