T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell transfer immunotherapy

Frontiers in Immunology

Immunology

Li-Feng Ran¹  Yan-Min Fan²  Fang-Lin Xie²  Ji-Zhu Xia²  Xun-Peng Xie³  Feng Wu⁴ 

[1] Clinical HIFU Center for Tumor Therapy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China;Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China;Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China;Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China;Department of Oncology, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, China;Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China;Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom;

关键词: high intensity focused ultrasound;    ablation;    liver cancer;    immunomodulation;    adoptive cell transfer;    immunotherapy;    apoptosis;    cytotoxic T lymphocyte;   

DOI  :  10.3389/fimmu.2023.1155229

 received in 2023-01-31, accepted in 2023-06-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundOur previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation.MethodsSixty H22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 106 T cells from HIFU treated-mice were intravenously injected into each syngeneic H22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer.ResultsT cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs (p < 0.001), with a significant increase of TNF-α (p < 0.001) and IFN-γ secretion (p < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand+ and perforin+ tumor-infiltrating lymphocytes (TILs) and apoptotic H22 tumor cells were significantly higher (p < 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand+ TILs (r = 0.9145, p < 0.001) and perforin+ TILs (r = 0.9619, p < 0.001).ConclusionT cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.

【 授权许可】

Unknown   
Copyright © 2023 Ran, Xie, Xia, Xie, Fan and Wu