Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy.

Abstract

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.

• Authors: Peng Peng, Yue Lou, Junjun Wang, Shicheng Wang, Ping Liu, Lisa X Xu
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 944115 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35874660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Peng, Lou, Wang, Wang, Liu and Xu.

Topics

• CD4-Positive T-Lymphocytes
• CD8-Positive T-Lymphocytes
• Immunologic Memory
• Immunotherapy
• Immunotherapy, Adoptive