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
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 ni...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/8/7018 |
| _version_ | 1797605129547939840 |
|---|---|
| author | Peishan Du Jiamin Zheng Shicheng Wang Yue Lou Zelu Zhang Junjun Wang Yongxin Zhu Jiaqi You Aili Zhang Ping Liu |
| author_facet | Peishan Du Jiamin Zheng Shicheng Wang Yue Lou Zelu Zhang Junjun Wang Yongxin Zhu Jiaqi You Aili Zhang Ping Liu |
| author_sort | Peishan Du |
| collection | DOAJ |
| description | 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<sup>+</sup> T-cell differentiation and enhancement of CD8<sup>+</sup> T-mediated tumor killing. In addition, CD4<sup>+</sup> 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. |
| first_indexed | 2024-03-11T04:56:47Z |
| format | Article |
| id | doaj.art-11fdb28a335845d9b269ba1e97c0c200 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:56:47Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-11fdb28a335845d9b269ba1e97c0c2002023-11-17T19:33:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248701810.3390/ijms24087018Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast CancerPeishan Du0Jiamin Zheng1Shicheng Wang2Yue Lou3Zelu Zhang4Junjun Wang5Yongxin Zhu6Jiaqi You7Aili Zhang8Ping Liu9School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, ChinaImmunosuppression 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<sup>+</sup> T-cell differentiation and enhancement of CD8<sup>+</sup> T-mediated tumor killing. In addition, CD4<sup>+</sup> 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.https://www.mdpi.com/1422-0067/24/8/7018cryo-thermal therapyIL-6mature MDSCs |
| spellingShingle | Peishan Du Jiamin Zheng Shicheng Wang Yue Lou Zelu Zhang Junjun Wang Yongxin Zhu Jiaqi You Aili Zhang Ping Liu 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 cryo-thermal therapy IL-6 mature MDSCs |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | cryo-thermal therapy IL-6 mature MDSCs |
| url | https://www.mdpi.com/1422-0067/24/8/7018 |
| work_keys_str_mv | AT peishandu combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT jiaminzheng combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT shichengwang combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT yuelou combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT zeluzhang combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT junjunwang combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT yongxinzhu combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT jiaqiyou combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT ailizhang combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer AT pingliu combiningcryothermaltherapywithantiil6treatmentpromotedthematurationofmdscstoinducelongtermsurvivalinamousemodelofbreastcancer |