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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Main Authors: Peng Peng, Yue Lou, Junjun Wang, Shicheng Wang, Ping Liu, Lisa X. Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Immunology
Subjects:
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.
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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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