Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8+ T effector cells of liver malignancies based on single cell transcriptomics

Ying Wang; Guang-Zhi Wang; Chao Chen; Hao-Zhe Huang; Yao-Hui Wang; Xin-Hong He; Lisa X Xu; Li-Chao Xu; Wen-Tao Li

doi:10.3389/fimmu.2023.1172362

Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8⁺ T effector cells of liver malignancies based on single cell transcriptomics

Front Immunol. 2023 Jun 2:14:1172362. doi: 10.3389/fimmu.2023.1172362. eCollection 2023.

Authors

Ying Wang^{1

2}, Guang-Zhi Wang^{3

4}, Chao Chen^{1

2}, Hao-Zhe Huang^{1

2}, Yao-Hui Wang^{1

2}, Xin-Hong He^{1

2}, Lisa X Xu³, Li-Chao Xu^{1

2}, Wen-Tao Li^{1

2}

Affiliations

¹ Department of Interventional Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
³ Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Medical Imaging Center, Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China.

Abstract

Introduction: Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies.

Methods: In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment.

Results: There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8⁺ effector T (CD8⁺ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway.

Conclusion: This study confirmed that MTT could more effectively activate peripheral CD8⁺ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.

Keywords: CD8+ effector T cells; liver cancer; multi-mode thermal therapy; radiofrequency ablation; single-cell RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Catheter Ablation*
Humans
Liver Neoplasms* / genetics
Liver Neoplasms* / therapy
Phosphatidylinositol 3-Kinases
Radiofrequency Ablation* / methods
Transcriptome

Substances

Phosphatidylinositol 3-Kinases

Grants and funding

This research was funded by the National Natural Science Foundation of China (Grant No. 82272095) and Zhangjiang National Innovation Demonstration Zone (Grant No. ZJ2021-ZD-007).