Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer

Du, Peishan; Zheng, Jiamin; Wang, Shicheng; Lou, Yue; Zhang, Zelu; Wang, Junjun; Zhu, Yongxin; You, Jiaqi; Zhang, Aili; Liu, Ping

doi:10.3390/ijms24087018

Open AccessArticle

Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer

by

Peishan Du

^†,

Jiamin Zheng

^†,

Shicheng Wang

,

Yue Lou

,

Zelu Zhang

,

Junjun Wang

,

Yongxin Zhu

,

Jiaqi You

,

Aili Zhang

and

Ping Liu

^*

School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(8), 7018; https://doi.org/10.3390/ijms24087018

Submission received: 8 March 2023 / Revised: 3 April 2023 / Accepted: 4 April 2023 / Published: 10 April 2023

(This article belongs to the Section Molecular Immunology)

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Abstract

Immunosuppression plays a significant role in tumor recurrence and metastasis, ultimately causing poor survival outcomes. Overcoming immunosuppression and stimulating durable antitumor immunity are essential for tumor treatment. In our previous study, a novel cryo-thermal therapy involving liquid nitrogen freezing and radiofrequency heating could reduce the proportion of Myeloid-derived suppressor cells (MDSCs), but the remaining MDSCs produced IL-6 by the NF-κB pathway, resulting in an impaired therapeutic effect. Therefore, here we combined cryo-thermal therapy with anti-IL-6 treatment to target the MDSC-dominant immunosuppressive environment, thereby optimizing the efficacy of cryo-thermal therapy. We found that combinational treatment significantly increased the long-term survival rate of breast cancer-bearing mice. Mechanistic investigation revealed that combination therapy was capable of reducing the proportion of MDSCs in the spleen and blood while promoting their maturation, which resulted in increased Th1-dominant CD4⁺ T-cell differentiation and enhancement of CD8⁺ T-mediated tumor killing. In addition, CD4⁺ Th1 cells promoted mature MDSCs to produce IL-7 through IFN-γ, indirectly contributing to the maintenance of Th1-dominant antitumor immunity in a positive feedback loop. Our work suggests an attractive immunotherapeutic strategy targeting the MDSC-dominant immunosuppressive environment, which would offer exciting opportunities for highly immunosuppressive and unresectable tumors in the clinic.

Keywords: cryo-thermal therapy; IL-6; mature MDSCs

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MDPI and ACS Style

Du, P.; Zheng, J.; Wang, S.; Lou, Y.; Zhang, Z.; Wang, J.; Zhu, Y.; You, J.; Zhang, A.; Liu, P. Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer. Int. J. Mol. Sci. 2023, 24, 7018. https://doi.org/10.3390/ijms24087018

AMA Style

Du P, Zheng J, Wang S, Lou Y, Zhang Z, Wang J, Zhu Y, You J, Zhang A, Liu P. Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer. International Journal of Molecular Sciences. 2023; 24(8):7018. https://doi.org/10.3390/ijms24087018

Chicago/Turabian Style

Du, Peishan, Jiamin Zheng, Shicheng Wang, Yue Lou, Zelu Zhang, Junjun Wang, Yongxin Zhu, Jiaqi You, Aili Zhang, and Ping Liu. 2023. "Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer" International Journal of Molecular Sciences 24, no. 8: 7018. https://doi.org/10.3390/ijms24087018

APA Style

Du, P., Zheng, J., Wang, S., Lou, Y., Zhang, Z., Wang, J., Zhu, Y., You, J., Zhang, A., & Liu, P. (2023). Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer. International Journal of Molecular Sciences, 24(8), 7018. https://doi.org/10.3390/ijms24087018

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Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer

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