Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy
Abstract Background Adoptive cell therapies (ACT) exhibit excellent efficacy in hematological malignancy. However, its application in solid tumors still has many challenges partly due to the tumor immune microenvironment. Cryo-thermal therapy (CTT) can induce an acute inflammatory response and remol...
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| Format: | Article |
| Language: | English |
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03884-2 |
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| author | Shicheng Wang Peng Peng Junjun Wang Zelu Zhang Ping Liu Lisa X. Xu |
| author_facet | Shicheng Wang Peng Peng Junjun Wang Zelu Zhang Ping Liu Lisa X. Xu |
| author_sort | Shicheng Wang |
| collection | DOAJ |
| description | Abstract Background Adoptive cell therapies (ACT) exhibit excellent efficacy in hematological malignancy. However, its application in solid tumors still has many challenges partly due to the tumor immune microenvironment. Cryo-thermal therapy (CTT) can induce an acute inflammatory response and remold the immune environment, providing an appropriate environment for the activation of adaptive immunity. However, it remains unclear whether CTT can enhance the efficacy of ACT. Methods A bilateral B16F10 tumor-bearing mouse model was used to assess whether CTT could enhance the efficacy of ACT. The right large tumor was subjected to CTT, and the left small tumor was collected for flow cytometry, RNA-seq, immunohistochemistry and TCR Vβ sequencing. Finally, bilateral B16F10 tumor-bearing mice and 4T1 tumor-bearing mice were used to assess the efficacy after CTT combined with ACT. Results CTT dramatically reshaped the immune microenvironment in distal tumors to an acute inflammatory state by promoting innate cell infiltration, increasing cytokine production by macrophages and DCs. The remodeling of the tumor immune microenvironment further enhanced the antitumor efficiency of ACT by increasing the proliferation of T cells, promoting activation of the effector functions of T cells and boosting the expansion of TCR clones. Conclusions Our results suggest that CTT can significantly reshape the tumor immunosuppressive microenvironment and convert “cold tumors” into “hot tumors,” thereby enhancing ACT-induced immune responses and maximizing the therapeutic effect of ACT. |
| format | Article |
| id | doaj-art-f37339bca3034075877ced61f71833f9 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-f37339bca3034075877ced61f71833f92025-02-02T12:26:42ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111410.1007/s00262-024-03884-2Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapyShicheng Wang0Peng Peng1Junjun Wang2Zelu Zhang3Ping Liu4Lisa X. Xu5School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong UniversityAbstract Background Adoptive cell therapies (ACT) exhibit excellent efficacy in hematological malignancy. However, its application in solid tumors still has many challenges partly due to the tumor immune microenvironment. Cryo-thermal therapy (CTT) can induce an acute inflammatory response and remold the immune environment, providing an appropriate environment for the activation of adaptive immunity. However, it remains unclear whether CTT can enhance the efficacy of ACT. Methods A bilateral B16F10 tumor-bearing mouse model was used to assess whether CTT could enhance the efficacy of ACT. The right large tumor was subjected to CTT, and the left small tumor was collected for flow cytometry, RNA-seq, immunohistochemistry and TCR Vβ sequencing. Finally, bilateral B16F10 tumor-bearing mice and 4T1 tumor-bearing mice were used to assess the efficacy after CTT combined with ACT. Results CTT dramatically reshaped the immune microenvironment in distal tumors to an acute inflammatory state by promoting innate cell infiltration, increasing cytokine production by macrophages and DCs. The remodeling of the tumor immune microenvironment further enhanced the antitumor efficiency of ACT by increasing the proliferation of T cells, promoting activation of the effector functions of T cells and boosting the expansion of TCR clones. Conclusions Our results suggest that CTT can significantly reshape the tumor immunosuppressive microenvironment and convert “cold tumors” into “hot tumors,” thereby enhancing ACT-induced immune responses and maximizing the therapeutic effect of ACT.https://doi.org/10.1007/s00262-024-03884-2Cryo-thermal therapyAdoptive cell therapySolid tumorTumor microenvironment |
| spellingShingle | Shicheng Wang Peng Peng Junjun Wang Zelu Zhang Ping Liu Lisa X. Xu Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy Cancer Immunology, Immunotherapy Cryo-thermal therapy Adoptive cell therapy Solid tumor Tumor microenvironment |
| title | Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy |
| title_full | Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy |
| title_fullStr | Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy |
| title_full_unstemmed | Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy |
| title_short | Cryo-thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy |
| title_sort | cryo thermal therapy reshaped the tumor immune microenvironment to enhance the efficacy of adoptive t cell therapy |
| topic | Cryo-thermal therapy Adoptive cell therapy Solid tumor Tumor microenvironment |
| url | https://doi.org/10.1007/s00262-024-03884-2 |
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