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Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response

BACKGROUND: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. PURPOSE: To identify the efficacy of T...

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Autores principales: Yang, Fei, Xu, Gui-Li, Huang, Jin-Tao, Yin, Yu, Xiang, Wei, Zhong, Bin-Yan, Li, Wan-Ci, Shen, Jian, Zhang, Shuai, Yang, Jun, Sun, Hong Peng, Wang, Wan-Sheng, Zhu, Xiao-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922415/
https://www.ncbi.nlm.nih.gov/pubmed/35300339
http://dx.doi.org/10.3389/fimmu.2022.847601
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author Yang, Fei
Xu, Gui-Li
Huang, Jin-Tao
Yin, Yu
Xiang, Wei
Zhong, Bin-Yan
Li, Wan-Ci
Shen, Jian
Zhang, Shuai
Yang, Jun
Sun, Hong Peng
Wang, Wan-Sheng
Zhu, Xiao-Li
author_facet Yang, Fei
Xu, Gui-Li
Huang, Jin-Tao
Yin, Yu
Xiang, Wei
Zhong, Bin-Yan
Li, Wan-Ci
Shen, Jian
Zhang, Shuai
Yang, Jun
Sun, Hong Peng
Wang, Wan-Sheng
Zhu, Xiao-Li
author_sort Yang, Fei
collection PubMed
description BACKGROUND: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. PURPOSE: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity. MATERIALS AND METHODS: This single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression. RESULTS: Fifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5–10.5) and PFS was 8.5 months (95% CI, 5.4–11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8(+), CD3(+) T cells and NK cells increased, the frequency of CD4(+)T cells and the CD4(+)/CD8(+) ratio decreased, and among them, CD8(+) T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response. CONCLUSION: TACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.
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spelling pubmed-89224152022-03-16 Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response Yang, Fei Xu, Gui-Li Huang, Jin-Tao Yin, Yu Xiang, Wei Zhong, Bin-Yan Li, Wan-Ci Shen, Jian Zhang, Shuai Yang, Jun Sun, Hong Peng Wang, Wan-Sheng Zhu, Xiao-Li Front Immunol Immunology BACKGROUND: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. PURPOSE: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity. MATERIALS AND METHODS: This single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression. RESULTS: Fifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5–10.5) and PFS was 8.5 months (95% CI, 5.4–11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8(+), CD3(+) T cells and NK cells increased, the frequency of CD4(+)T cells and the CD4(+)/CD8(+) ratio decreased, and among them, CD8(+) T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response. CONCLUSION: TACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers. Frontiers Media S.A. 2022-02-18 /pmc/articles/PMC8922415/ /pubmed/35300339 http://dx.doi.org/10.3389/fimmu.2022.847601 Text en Copyright © 2022 Yang, Xu, Huang, Yin, Xiang, Zhong, Li, Shen, Zhang, Yang, Sun, Wang and Zhu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yang, Fei
Xu, Gui-Li
Huang, Jin-Tao
Yin, Yu
Xiang, Wei
Zhong, Bin-Yan
Li, Wan-Ci
Shen, Jian
Zhang, Shuai
Yang, Jun
Sun, Hong Peng
Wang, Wan-Sheng
Zhu, Xiao-Li
Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response
title Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response
title_full Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response
title_fullStr Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response
title_full_unstemmed Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response
title_short Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response
title_sort transarterial chemoembolization combined with immune checkpoint inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: efficacy and systemic immune response
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922415/
https://www.ncbi.nlm.nih.gov/pubmed/35300339
http://dx.doi.org/10.3389/fimmu.2022.847601
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