Guo Y, Li RC, Xia WL, Yang X, Zhu WB, Li FT, Hu HT, Li HL. Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16(7): 3256-3269 [PMID: 39072154 DOI: 10.4251/wjgo.v16.i7.3256]
Corresponding Author of This Article
Hai-Liang Li, MD, Chief Doctor, Department of Minimal Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No. 127 Dongming Road, Zhengzhou 450003, Henan Province, China. lihailianggy@163.com
Research Domain of This Article
Immunology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3256-3269 Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3256
Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma
Yuan Guo, Wei-Li Xia, Xiong Yang, Wen-Bo Zhu, Fang-Ting Li, Hong-Tao Hu, Hai-Liang Li, Department of Minimal Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450003, Henan Province, China
Ru-Chun Li, Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450003, Henan Province, China
Co-first authors: Yuan Guo and Ru-Chun Li.
Co-corresponding authors: Hong-Tao Hu and Hai-Liang Li.
Author contributions: Guo Y and Li HL created the research design; Guo Y and Li RC wrote and edited the manuscript; Xia WL and Yang X collected the data; Zhu WB and Li FT performed the data analysis; Li HL and Hu HT conceptualized and supervised the study; and all the authors have read and approved the final version of the manuscript. Considering the author’s contribution to this study, Guo Y and Li RC are the co-first author, Hu HT and Li HL are the co-corresponding author.
Supported byHenan Province Natural Science Foundation, No. 212300410403; and Medical Education Research Project of Henan Province, No. Wjlx2021334.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of Henan Cancer Hospital (approval number: 2017002).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Experiment Ethics Committee of Hubei Provincial Center for Disease Control and Prevention (approval number: 202310157).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated and/or analyzed in the current study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai-Liang Li, MD, Chief Doctor, Department of Minimal Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No. 127 Dongming Road, Zhengzhou 450003, Henan Province, China. lihailianggy@163.com
Received: March 6, 2024 Revised: May 3, 2024 Accepted: May 17, 2024 Published online: July 15, 2024 Processing time: 127 Days and 19.4 Hours
Abstract
BACKGROUND
The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC.
AIM
To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment.
METHODS
Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry.
RESULTS
Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC.
CONCLUSION
TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.
Core Tip: This study revealed that the combination of transcatheter arterial chemoembolization and donafinib or lenvatinib may be relatively beneficial in improving the immune suppression status of patients and inducing relatively robust anti-tumor immune responses. In addition, certain immune cells and protein molecules are significantly correlated with the prognosis of patients. The study results provide patients with reference for their selection of combination therapy strategies and help them predict their clinical prognosis.
