Tumor Treatment System with Alternate Cooling and Heating - Preliminary Results in an Animal Model

Sun, Junqiang; Xu, Chunjie; Wei, Guanghua; Sun, Xiao; Liu, P.; Zhang, A. L.; Xu, Lisa X.

doi:10.1007/978-3-642-03906-5_93

Cited by 7 publications

(5 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tumor was induced by injection of 5×10 5 4T1 cells subcutaneously into the right dorsal region of mouse and received cryo-thermal therapy 3 weeks later, reaching the size of ~10 mm in diameter. Cryo-thermal therapy was performed using a modified protocol 11 . Briefly, a thermocouple was inserted to the bottom of tumor to monitor the local temperature in real time.…”

Section: Methodsmentioning

confidence: 99%

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

Xue¹,

Liu²,

Zhou³

et al. 2016

Theranostics

View full text Add to dashboard Cite

Cryo-thermal therapy has been emerged as a promising novel therapeutic strategy for advanced breast cancer, triggering higher incidence of tumor regression and enhanced remission of metastasis than routine treatments. To better understand its anti-tumor mechanism, we utilized a spontaneous metastatic mouse model and quantitative proteomics to compare N-glycoproteome changes in 94 serum samples with and without treatment. We quantified 231 highly confident N-glycosylated proteins using iTRAQ shotgun proteomics. Among them, 53 showed significantly discriminated regulatory patterns over the time course, in which the acute phase response emerged as the most enhanced pathway. The anti-tumor feature of the acute response was further investigated using parallel reaction monitoring target proteomics and flow cytometry on 23 of the 53 significant proteins. We found that cryo-thermal therapy reset the tumor chronic inflammation to an “acute” phenotype, with up-regulation of acute phase proteins including IL-6 as a key regulator. The IL-6 mediated “acute” phenotype transformed IL-4 and Treg-promoting ICOSL expression to Th1-promoting IFN-γ and IL-12 production, augmented complement system activation and CD86+MHCII+ dendritic cells maturation and enhanced the proliferation of Th1 memory cells. In addition, we found an increased production of tumor progression and metastatic inhibitory proteins under such “acute” environment, favoring the anti-metastatic effect. Moreover, cryo-thermal on tumors induced the strongest “acute” response compared to cryo/hyperthermia alone or cryo-thermal on healthy tissues, accompanying by the most pronounced anti-tumor immunological effect. In summary, we demonstrated that cryo-thermal therapy induced, IL-6 mediated “acute” microenvironment shifted the tumor chronic microenvironment from Th2 immunosuppressive and pro-tumorigenic to Th1 immunostimulatory and tumoricidal state. Moreover, the magnitude of “acute” and “danger” signals play a key role in determining the efficacy of anti-tumor activity.

show abstract

Section: Methodsmentioning

confidence: 99%

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

Xue¹,

Liu²,

Zhou³

et al. 2016

Theranostics

View full text Add to dashboard Cite

show abstract

“…In our previous study, we develop a novel cryo-thermal therapy through applying local rapid cooling followed by rapid heating of tumor tissue, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma and murine B16 melanoma model [18][19][20][21][22][23][24]. Cryo-thermal therapy induces CD4 þ T cells to orchestrate anti-tumor immune memory response leading to long-term tumor-free survival [25].…”

Section: Introductionmentioning

confidence: 99%

Cryo-thermal therapy inducing MI macrophage polarization created CXCL10 and IL-6-rich pro-inflammatory environment for CD4⁺T cell-mediated anti-tumor immunity

Liu

Jia

Lou

et al. 2019

International Journal of Hyperthermia

View full text Add to dashboard Cite

show abstract

“…The cryo-thermal therapy procedure was carried out as previously reported [14][15][16]. Briefly, the cryo-thermal therapy system was composed of liquid nitrogen for cooling and radiofrequency for heating.…”

Section: Cryo-thermal Therapy Proceduresmentioning

confidence: 99%

“…During this process, the released tumor antigens and chaperones recruit innate immune cells and, subsequently, activate T cells, stimulating systemic antitumor immune responses [9,12,13]. Previously, we developed a novel cryo-thermal therapy for tumors through alternative cooling and heating of tumor tissue in animal models [14][15][16]. After cryo-thermal therapy, tumors release tumor antigens and danger signals in situ, which facilitates a durable antitumor adaptive immune response [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy

Cen

Lou

Wang

et al. 2021

IJMS

View full text Add to dashboard Cite

Effective cancer therapies should reshape immunosuppression and trigger antitumor immunity. Previously, we developed a novel cryo-thermal therapy through applying local rapid cooling followed by rapid heating of tumor tissue. It could not only ablate local tumors, but also, subsequently, induce systemic long-term antitumor immunity. Hyperthermia can induce the release of extracellular vesicles (EVs) to stimulate antitumor immunity. We examine whether EVs are released after cryo-thermal therapy and whether they could improve the efficacy of cryo-thermal therapy in the 4T1 model. In this study, serum extracellular vesicles (sEVs) are isolated and characterized 3 h after cryo-thermal therapy of subcutaneous tumors. sEV phagocytosis is observed in vitro and in vivo by using laser confocal microscopy and flow cytometry. After cryo-thermal therapy, sEVs are administered to mice via the tail vein, and changes in immune cells are investigated by using flow cytometry. After cryo-thermal therapy, a large number of sEVs are released to the periphery carrying danger signals and tumor antigens, and these sEVs could be phagocytosed by peripheral blood monocytes and differentiated macrophages. After cryo-thermal therapy, supplementation with sEVs released after treatment promotes the differentiation of myeloid-derived suppressor cells (MDSCs), monocytes into macrophages and CD4+ T cells into the Th1 subtype, as well as prolonging the long-term survival of the 4T1 subcutaneous tumor-bearing mice. sEVs released after cryo-thermal tumor treatment could clinically serve as an adjuvant in subsequent cryo-thermal therapy to improve the therapeutic effects on malignant tumors.

show abstract

Tumor Treatment System with Alternate Cooling and Heating - Preliminary Results in an Animal Model

Cited by 7 publications

References 13 publications

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

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

Cryo-thermal therapy inducing MI macrophage polarization created CXCL10 and IL-6-rich pro-inflammatory environment for CD4⁺T cell-mediated anti-tumor immunity

Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy

Contact Info

Product

Resources

About

Tumor Treatment System with Alternate Cooling and Heating - Preliminary Results in an Animal Model

Cited by 7 publications

References 13 publications

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

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

Cryo-thermal therapy inducing MI macrophage polarization created CXCL10 and IL-6-rich pro-inflammatory environment for CD4+T cell-mediated anti-tumor immunity

Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy

Contact Info

Product

Resources

About

Cryo-thermal therapy inducing MI macrophage polarization created CXCL10 and IL-6-rich pro-inflammatory environment for CD4⁺T cell-mediated anti-tumor immunity