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Downregulated TNF-α Levels after Cryo-Thermal Therapy Drive Tregs Fragility to Promote Long-Term Antitumor Immunity

Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
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Authors to whom correspondence should be addressed.
Academic Editor: Donald J. Buchsbaum
Int. J. Mol. Sci. 2021, 22(18), 9951; https://doi.org/10.3390/ijms22189951
Received: 17 August 2021 / Revised: 4 September 2021 / Accepted: 9 September 2021 / Published: 15 September 2021
(This article belongs to the Section Molecular Biology)
Immunotherapy has emerged as a therapeutic pillar in tumor treatment, but only a minority of patients get benefit. Overcoming the limitations of immunosuppressive environment is effective for immunotherapy. Moreover, host T cell activation and longevity within tumor are required for the long-term efficacy. In our previous study, a novel cryo-thermal therapy was developed to improve long-term survival in B16F10 melanoma and s.q. 4T1 breast cancer mouse models. We determined that cryo-thermal therapy induced Th1-dominant CD4+ T cell differentiation and the downregulation of Tregs in B16F10 model, contributing to tumor-specific and long-lasting immune protection. However, whether cryo-thermal therapy can affect the differentiation and function of T cells in a s.q. 4T1 model remains unknown. In this study, we also found that cryo-thermal therapy induced Th1-dominant differentiation of CD4+ T cells and the downregulation of effector Tregs. In particular, cryo-thermal therapy drove the fragility of Tregs and impaired their function. Furthermore, we discovered the downregulated level of serum tumor necrosis factor-α at the late stage after cryo-thermal therapy which played an important role in driving Treg fragility. Our findings revealed that cryo-thermal therapy could reprogram the suppressive environment and induce strong and durable antitumor immunity, which facilitate the development of combination strategies in immunotherapy. View Full-Text
Keywords: cryo-thermal therapy; Treg fragility; TNF-α cryo-thermal therapy; Treg fragility; TNF-α
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MDPI and ACS Style

Lou, Y.; Wang, J.; Peng, P.; Wang, S.; Liu, P.; Xu, L.X. Downregulated TNF-α Levels after Cryo-Thermal Therapy Drive Tregs Fragility to Promote Long-Term Antitumor Immunity. Int. J. Mol. Sci. 2021, 22, 9951. https://doi.org/10.3390/ijms22189951

AMA Style

Lou Y, Wang J, Peng P, Wang S, Liu P, Xu LX. Downregulated TNF-α Levels after Cryo-Thermal Therapy Drive Tregs Fragility to Promote Long-Term Antitumor Immunity. International Journal of Molecular Sciences. 2021; 22(18):9951. https://doi.org/10.3390/ijms22189951

Chicago/Turabian Style

Lou, Yue, Junjun Wang, Peng Peng, Shicheng Wang, Ping Liu, and Lisa X. Xu 2021. "Downregulated TNF-α Levels after Cryo-Thermal Therapy Drive Tregs Fragility to Promote Long-Term Antitumor Immunity" International Journal of Molecular Sciences 22, no. 18: 9951. https://doi.org/10.3390/ijms22189951

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