冷冻热疗后 Th1 优势 CD4(+) T 细胞协调内源性系统性抗肿瘤免疫记忆

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.