Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy
Recent studies suggest that highly activated, polyfunctional CD4+ T cells are incredibly effective in strengthening and sustaining overall host antitumor immunity, promoting tumor-specific CD4+ T-cell responses and effectively enhancing antitumor immunity by immunotherapy. Previously, we developed a...
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Frontiers Media S.A.
2022-07-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.944115/full |
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author | Peng Peng Yue Lou Junjun Wang Shicheng Wang Ping Liu Lisa X. Xu |
author_facet | Peng Peng Yue Lou Junjun Wang Shicheng Wang Ping Liu Lisa X. Xu |
author_sort | Peng Peng |
collection | DOAJ |
description | Recent studies suggest that highly activated, polyfunctional CD4+ T cells are incredibly effective in strengthening and sustaining overall host antitumor immunity, promoting tumor-specific CD4+ T-cell responses and effectively enhancing antitumor immunity by immunotherapy. Previously, we developed a novel cryo-thermal therapy for local tumor ablation and achieved long-term survival rates in several tumor models. It was discovered that cryo-thermal therapy remodeled the tumor microenvironment and induced an antigen-specific CD4+ T-cell response, which mediated stronger antitumor immunity in vivo. In this study, the phenotype of bulk T cells in spleen was analyzed by flow cytometry after cryo-thermal therapy and both CD4+ Th1 and CD8+ CTL were activated. In addition, by using T-cell depletion, isolation, and adoptive T-cell therapy, it was found that cryo-thermal therapy induced Th1-dominant CD4+ T cells that directly inhibited the growth of tumor cells, promoted the maturation of MDSCs via CD4+ T-cell-derived IFN-γ and enhanced the cytotoxic effector function of NK cells and CD8+ T cells, and promoted the maturation of APCs via cell-cell contact and CD4+ T-cell-derived IFN-γ. Considering the multiple roles of cryo-thermal-induced Th1-dominant CD4+ T cells in augmenting antitumor immune memory, we suggest that local cryo-thermal therapy is an attractive thermo-immunotherapy strategy to harness host antitumor immunity and has great potential for clinical application. |
first_indexed | 2024-04-13T22:10:30Z |
format | Article |
id | doaj.art-ea3608053d0b44c0bef4f4f4b8c19949 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-13T22:10:30Z |
publishDate | 2022-07-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
spelling | doaj.art-ea3608053d0b44c0bef4f4f4b8c199492022-12-22T02:27:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.944115944115Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal TherapyPeng PengYue LouJunjun WangShicheng WangPing LiuLisa X. XuRecent studies suggest that highly activated, polyfunctional CD4+ T cells are incredibly effective in strengthening and sustaining overall host antitumor immunity, promoting tumor-specific CD4+ T-cell responses and effectively enhancing antitumor immunity by immunotherapy. Previously, we developed a novel cryo-thermal therapy for local tumor ablation and achieved long-term survival rates in several tumor models. It was discovered that cryo-thermal therapy remodeled the tumor microenvironment and induced an antigen-specific CD4+ T-cell response, which mediated stronger antitumor immunity in vivo. In this study, the phenotype of bulk T cells in spleen was analyzed by flow cytometry after cryo-thermal therapy and both CD4+ Th1 and CD8+ CTL were activated. In addition, by using T-cell depletion, isolation, and adoptive T-cell therapy, it was found that cryo-thermal therapy induced Th1-dominant CD4+ T cells that directly inhibited the growth of tumor cells, promoted the maturation of MDSCs via CD4+ T-cell-derived IFN-γ and enhanced the cytotoxic effector function of NK cells and CD8+ T cells, and promoted the maturation of APCs via cell-cell contact and CD4+ T-cell-derived IFN-γ. Considering the multiple roles of cryo-thermal-induced Th1-dominant CD4+ T cells in augmenting antitumor immune memory, we suggest that local cryo-thermal therapy is an attractive thermo-immunotherapy strategy to harness host antitumor immunity and has great potential for clinical application.https://www.frontiersin.org/articles/10.3389/fimmu.2022.944115/fulltumor ablationcryo-thermal therapyantitumor immunityCD4+ T cellsTh1IFN-γ |
spellingShingle | Peng Peng Yue Lou Junjun Wang Shicheng Wang Ping Liu Lisa X. Xu Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy Frontiers in Immunology tumor ablation cryo-thermal therapy antitumor immunity CD4+ T cells Th1 IFN-γ |
title | Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy |
title_full | Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy |
title_fullStr | Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy |
title_full_unstemmed | Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy |
title_short | Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy |
title_sort | th1 dominant cd4 t cells orchestrate endogenous systematic antitumor immune memory after cryo thermal therapy |
topic | tumor ablation cryo-thermal therapy antitumor immunity CD4+ T cells Th1 IFN-γ |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.944115/full |
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