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肝癌肿瘤切除可恢复循环中的调节性T细胞。

Tumor Resection in Hepatic Carcinomas Restores Circulating T Regulatory Cells.

作者信息

Martín-Sierra Carmen, Martins Ricardo, Coucelo Margarida, Abrantes Ana Margarida, Caetano Oliveira Rui, Tralhão José Guilherme, Botelho Maria Filomena, Furtado Emanuel, Domingues Maria Rosário, Paiva Artur, Laranjeira Paula

机构信息

Flow Cytometry Unit, Department of Clinical Pathology, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, 3000-076 Coimbra, Portugal.

Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal.

出版信息

J Clin Med. 2024 Oct 9;13(19):6011. doi: 10.3390/jcm13196011.

DOI:10.3390/jcm13196011
PMID:39408071
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC11478317/
Abstract

: Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) represent major primary liver cancers, affecting one of the most vital organs in the human body. T regulatory (Treg) cells play an important role in liver cancers through the immunosuppression of antitumor immune responses. The current study focuses on the characterization of circulating natural killer (NK) cells and T cell subsets, including Treg cells, in CCA and HCC patients, before and after surgical tumor resection, in order to understand the effect of tumor resection on the homeostasis of peripheral blood NK cells and T cells. : Whole blood assays were performed to monitor immune alterations and the functional competence of circulating lymphocytes in a group of ten healthy individuals, eight CCA patients, and twenty HCC patients, before and one month after the surgical procedure, using flow cytometry, cell sorting, and qRT-PCR. : Before tumor resection, both HCC and CCA patients display increased percentages of CD8 Treg cells and decreased frequencies of circulating CD4 Treg cells. Notwithstanding, no functional impairment was detected on circulating CD4 Treg cells, neither in CCA nor in HCC patients. Interestingly, the frequency of peripheral CD4 Treg cells increased from 0.55% ± 0.49 and 0.71% ± 0.54 (in CCA and HCC, respectively) at T0 to 0.99% ± 0.91 and 1.17% ± 0.33 (in CCA and HCC, respectively) at T1, following tumor resection. : Our results suggest mechanisms of immune modulation induced by tumor resection.

摘要

胆管癌(CCA)和肝细胞癌(HCC)是主要的原发性肝癌,影响着人体最重要的器官之一。调节性T(Treg)细胞通过对抗肿瘤免疫反应的免疫抑制在肝癌中发挥重要作用。本研究聚焦于CCA和HCC患者手术切除肿瘤前后循环自然杀伤(NK)细胞和T细胞亚群(包括Treg细胞)的特征,以了解肿瘤切除对外周血NK细胞和T细胞稳态的影响。

对一组10名健康个体、8名CCA患者和20名HCC患者在手术前及手术后1个月进行全血检测,采用流式细胞术、细胞分选和qRT-PCR监测免疫变化及循环淋巴细胞的功能能力。

在肿瘤切除前,HCC和CCA患者的CD8 Treg细胞百分比均增加,循环CD4 Treg细胞频率均降低。尽管如此,在CCA和HCC患者中,循环CD4 Treg细胞均未检测到功能损害。有趣的是,肿瘤切除后,外周CD4 Treg细胞频率从T0时的0.55%±0.49和0.71%±0.54(分别在CCA和HCC中)增加到T1时的0.99%±0.91和1.17%±0.33(分别在CCA和HCC中)。

我们的结果提示了肿瘤切除诱导的免疫调节机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba7/11478317/3c44fa124eaf/jcm-13-06011-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba7/11478317/a64a54205dca/jcm-13-06011-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba7/11478317/3c44fa124eaf/jcm-13-06011-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba7/11478317/a64a54205dca/jcm-13-06011-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba7/11478317/3c44fa124eaf/jcm-13-06011-g002.jpg

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本文引用的文献

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Inequities in primary liver cancer in Europe: The state of play.欧洲原发性肝癌的不平等现象:现状。
J Hepatol. 2024 Apr;80(4):645-660. doi: 10.1016/j.jhep.2023.12.031. Epub 2024 Jan 17.
2
FOXP3 regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity.干扰素 γ-STAT1-IFITM3 反馈回路介导的 FOXP3 调节性 T 细胞扰动对于抗肿瘤免疫至关重要。
Nat Commun. 2024 Jan 2;15(1):122. doi: 10.1038/s41467-023-44391-9.
3
Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma.
HBV 感染进展为 HBV 肝硬化和 HBV 相关肝细胞癌过程中免疫细胞的单细胞全景。
Front Immunol. 2023 Dec 5;14:1320414. doi: 10.3389/fimmu.2023.1320414. eCollection 2023.
4
The dual role of regulatory T cells in hepatitis B virus infection and related hepatocellular carcinoma.调节性T细胞在乙型肝炎病毒感染及相关肝细胞癌中的双重作用
Immunology. 2024 Apr;171(4):445-463. doi: 10.1111/imm.13738. Epub 2023 Dec 14.
5
Identification of cancer-associated fibroblasts signature for predicting the prognosis and immunotherapy response in hepatocellular carcinoma.鉴定癌症相关成纤维细胞特征,预测肝细胞癌的预后和免疫治疗反应。
Medicine (Baltimore). 2023 Nov 10;102(45):e35938. doi: 10.1097/MD.0000000000035938.
6
Identification of M2-like macrophage-related signature for predicting the prognosis, ecosystem and immunotherapy response in hepatocellular carcinoma.鉴定 M2 样巨噬细胞相关特征,用于预测肝细胞癌的预后、生态系统和免疫治疗反应。
PLoS One. 2023 Sep 19;18(9):e0291645. doi: 10.1371/journal.pone.0291645. eCollection 2023.
7
The clinicopathological significance and relapse predictive role of tumor microenvironment of intrahepatic cholangiocarcinoma after radical surgery.根治性手术后肝内胆管癌肿瘤微环境的临床病理意义及复发预测作用。
Cancer. 2023 Feb 1;129(3):393-404. doi: 10.1002/cncr.34552. Epub 2022 Nov 26.
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