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Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence

BACKGROUND: Thermal therapy induces an immune response in patients with hepatocellular carcinoma (HCC), but the dynamic characteristics of the natural killer (NK) cell immune response post-thermal ablation remain unclear. We conducted a prospective longitudinal cohort study to observe the dynamic ch...

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Autores principales: Wang, Hai-Yan, Cui, Xiong-Wei, Zhang, Yong-Hong, Chen, Yu, Lu, Ning-Ning, Bai, Li, Duan, Zhong-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10228897/
https://www.ncbi.nlm.nih.gov/pubmed/37254046
http://dx.doi.org/10.1186/s12885-023-10823-4
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author Wang, Hai-Yan
Cui, Xiong-Wei
Zhang, Yong-Hong
Chen, Yu
Lu, Ning-Ning
Bai, Li
Duan, Zhong-Ping
author_facet Wang, Hai-Yan
Cui, Xiong-Wei
Zhang, Yong-Hong
Chen, Yu
Lu, Ning-Ning
Bai, Li
Duan, Zhong-Ping
author_sort Wang, Hai-Yan
collection PubMed
description BACKGROUND: Thermal therapy induces an immune response in patients with hepatocellular carcinoma (HCC), but the dynamic characteristics of the natural killer (NK) cell immune response post-thermal ablation remain unclear. We conducted a prospective longitudinal cohort study to observe the dynamic changes of phenotype and function of NK cells in peripheral blood before and after thermal ablation of hepatitis B-associated HCC and their correlation with tumor recurrence. METHODS: Fifty-six patients clinically and pathologically confirmed with hepatitis B-associated HCC were selected for thermal ablation. Peripheral blood was collected on day 0, day 7, and month 1. NK cell subsets, receptors, and killing function were detected by flow cytometry, and the LDH levels were examined. Overall recurrence and associated variables were estimated using Kaplan–Meier, log-rank, and Cox proportional-hazards analyses. RESULTS: The frequency of CD3(−)CD56(+) cells was increased on day 7 (P < 0.01) without significant differences between D0 and M1. NKG2D, NKp44, NKp30, CD159a, and CD158a expression was increased on M1 (all P < 0.05). The granzyme B and IFN-γ expression in NK cells were higher on M1 vs. D0 (P < 0.05). On day 7, the NK cell lysis activity of the target K562 cells was increased (P < 0.01) but decreased on M1 (P < 0.05). Survival analysis showed that CD158a expression and IFN-γ and perforin release on day 0 were associated with the risk of HCC recurrence. Cox regression analysis showed that the expression changes in CD56, NKp46, granzyme B, and perforin (D7-D0) induced by thermal ablation were associated with recurrence-free survival (RFS) of patients with HCC. CONCLUSION: Thermal ablation increased the frequency and function of CD3(−)CD56(+) NK cells in the peripheral blood of patients with HCC. These cells tended to be more differentiated and activated. Notably, expression levels of NK cell receptors NKp46, perforin, and granzyme B were associated with RFS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10823-4.
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spelling pubmed-102288972023-06-01 Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence Wang, Hai-Yan Cui, Xiong-Wei Zhang, Yong-Hong Chen, Yu Lu, Ning-Ning Bai, Li Duan, Zhong-Ping BMC Cancer Research BACKGROUND: Thermal therapy induces an immune response in patients with hepatocellular carcinoma (HCC), but the dynamic characteristics of the natural killer (NK) cell immune response post-thermal ablation remain unclear. We conducted a prospective longitudinal cohort study to observe the dynamic changes of phenotype and function of NK cells in peripheral blood before and after thermal ablation of hepatitis B-associated HCC and their correlation with tumor recurrence. METHODS: Fifty-six patients clinically and pathologically confirmed with hepatitis B-associated HCC were selected for thermal ablation. Peripheral blood was collected on day 0, day 7, and month 1. NK cell subsets, receptors, and killing function were detected by flow cytometry, and the LDH levels were examined. Overall recurrence and associated variables were estimated using Kaplan–Meier, log-rank, and Cox proportional-hazards analyses. RESULTS: The frequency of CD3(−)CD56(+) cells was increased on day 7 (P < 0.01) without significant differences between D0 and M1. NKG2D, NKp44, NKp30, CD159a, and CD158a expression was increased on M1 (all P < 0.05). The granzyme B and IFN-γ expression in NK cells were higher on M1 vs. D0 (P < 0.05). On day 7, the NK cell lysis activity of the target K562 cells was increased (P < 0.01) but decreased on M1 (P < 0.05). Survival analysis showed that CD158a expression and IFN-γ and perforin release on day 0 were associated with the risk of HCC recurrence. Cox regression analysis showed that the expression changes in CD56, NKp46, granzyme B, and perforin (D7-D0) induced by thermal ablation were associated with recurrence-free survival (RFS) of patients with HCC. CONCLUSION: Thermal ablation increased the frequency and function of CD3(−)CD56(+) NK cells in the peripheral blood of patients with HCC. These cells tended to be more differentiated and activated. Notably, expression levels of NK cell receptors NKp46, perforin, and granzyme B were associated with RFS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10823-4. BioMed Central 2023-05-30 /pmc/articles/PMC10228897/ /pubmed/37254046 http://dx.doi.org/10.1186/s12885-023-10823-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Hai-Yan
Cui, Xiong-Wei
Zhang, Yong-Hong
Chen, Yu
Lu, Ning-Ning
Bai, Li
Duan, Zhong-Ping
Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence
title Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence
title_full Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence
title_fullStr Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence
title_full_unstemmed Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence
title_short Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence
title_sort dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis b associated hepatocellular carcinoma and their correlation with tumor recurrence
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10228897/
https://www.ncbi.nlm.nih.gov/pubmed/37254046
http://dx.doi.org/10.1186/s12885-023-10823-4
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