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Higher frequencies of GARP(+)CTLA-4(+)Foxp3(+) T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality.肝癌患者中 GARP(+)CTLA-4(+)Foxp3(+) T 调节细胞和髓源抑制细胞的频率较高与 T 细胞功能受损有关。
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Randomized, prospective, comparative study on the effects and safety of sorafenib vs. hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis.随机、前瞻性、比较研究索拉非尼与肝动脉灌注化疗治疗伴有门静脉癌栓的晚期肝细胞癌的疗效和安全性。
Cancer Chemother Pharmacol. 2018 Sep;82(3):469-478. doi: 10.1007/s00280-018-3638-0. Epub 2018 Jul 7.

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Immun Inflamm Dis. 2024 Sep;12(9):e70007. doi: 10.1002/iid3.70007.
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Interventional therapy combined with tyrosine kinase inhibitors with or without immune checkpoint inhibitors as initial treatment for hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis.介入治疗联合酪氨酸激酶抑制剂(伴或不伴免疫检查点抑制剂)作为门静脉肿瘤血栓形成的肝细胞癌的初始治疗:一项系统评价和荟萃分析
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Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.免疫耐受机制对原发性和继发性肝癌免疫治疗疗效的影响。
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本文引用的文献

1
Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected.肿瘤微环境中的髓源性抑制细胞:意料之外,情理之中。
J Clin Invest. 2015 Sep;125(9):3356-64. doi: 10.1172/JCI80005. Epub 2015 Jul 13.
2
Immunological features of T cells induced by human telomerase reverse transcriptase-derived peptides in patients with hepatocellular carcinoma.端粒酶逆转录酶衍生肽诱导的肝癌患者 T 细胞的免疫学特征。
Cancer Lett. 2015 Aug 10;364(2):98-105. doi: 10.1016/j.canlet.2015.04.031. Epub 2015 May 14.
3
Using chemo-drugs or irradiation to break immune tolerance and facilitate immunotherapy in solid cancer.使用化疗药物或放疗来打破免疫耐受并促进实体癌的免疫治疗。
Cell Immunol. 2015 Mar;294(1):54-9. doi: 10.1016/j.cellimm.2015.02.003. Epub 2015 Feb 10.
4
Blood neutrophil to lymphocyte ratio as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy.血中性粒细胞与淋巴细胞比值作为接受肝动脉灌注化疗的晚期肝细胞癌患者的预测指标
Hepatol Res. 2015 Sep;45(9):949-959. doi: 10.1111/hepr.12436. Epub 2014 Nov 17.
5
Adverse immunoregulatory effects of 5FU and CPT11 chemotherapy on myeloid-derived suppressor cells and colorectal cancer outcomes.5FU 和 CPT11 化疗对髓源性抑制细胞的免疫调节作用及对结直肠癌结局的影响。
Cancer Res. 2014 Nov 1;74(21):6022-35. doi: 10.1158/0008-5472.CAN-14-0657. Epub 2014 Sep 10.
6
Neutrophil-lymphocyte ratio is a simple and novel biomarker for prediction of survival after radioembolization for metastatic colorectal cancer.中性粒细胞与淋巴细胞比值是一种简单且新颖的生物标志物,用于预测转移性结直肠癌经放射性栓塞治疗后的生存率。
Ann Surg Oncol. 2015 May;22(5):1701-7. doi: 10.1245/s10434-014-4050-6. Epub 2014 Sep 5.
7
Blood neutrophil-lymphocyte ratio predicts survival in patients with advanced pancreatic cancer treated with chemotherapy.血液中性粒细胞与淋巴细胞比值可预测接受化疗的晚期胰腺癌患者的生存率。
Ann Surg Oncol. 2015 Feb;22(2):670-6. doi: 10.1245/s10434-014-4021-y. Epub 2014 Aug 26.
8
A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis.索拉非尼与肝动脉灌注化疗治疗伴有门静脉癌栓的晚期肝细胞癌的对比研究。
J Gastroenterol. 2015 Apr;50(4):445-54. doi: 10.1007/s00535-014-0978-3. Epub 2014 Jul 16.
9
Chemotherapeutic targeting of cancer-induced immunosuppressive cells.癌症诱导免疫抑制细胞的化学治疗靶向。
Cancer Res. 2014 May 15;74(10):2663-8. doi: 10.1158/0008-5472.CAN-14-0301. Epub 2014 Apr 28.
10
IL-17A produced by γδ T cells promotes tumor growth in hepatocellular carcinoma.γδ T 细胞产生的白介素-17A 促进肝癌肿瘤生长。
Cancer Res. 2014 Apr 1;74(7):1969-82. doi: 10.1158/0008-5472.CAN-13-2534. Epub 2014 Feb 13.

髓源性抑制细胞与肝细胞癌肝动脉灌注化疗患者的预后相关。

Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma.

作者信息

Mizukoshi Eishiro, Yamashita Tatsuya, Arai Kuniaki, Terashima Takeshi, Kitahara Masaaki, Nakagawa Hidetoshi, Iida Noriho, Fushimi Kazumi, Kaneko Shuichi

机构信息

Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan.

出版信息

Cancer Immunol Immunother. 2016 Jun;65(6):715-25. doi: 10.1007/s00262-016-1837-2. Epub 2016 Apr 15.

DOI:10.1007/s00262-016-1837-2
PMID:27083166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11029544/
Abstract

Hepatic arterial infusion chemotherapy (HAIC) has been employed as an alternative therapy to sorafenib for the patients with advanced hepatocellular carcinoma (HCC). In this study, we performed a comparative analysis of various immune cell responses including tumor-associated antigen (TAA)-specific T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in advanced HCC patients treated with HAIC. Thirty-six HCC patients were examined in the study. Interferon gamma enzyme-linked immunospot assays were performed to examine the frequency of TAA-specific T cells. The frequencies of Tregs and MDSCs were examined by multicolor fluorescence-activated cell sorting analysis. The treatment with HAIC using interferon (IFN)/5-fluorouracil (FU) or IFN/FU + cisplatin modulated the frequencies of various immune cells. In 22.2 % of patients, the frequency of TAA-specific T cells increased after HAIC. Although the frequency of Tregs decreased after HAIC, it was not associated with the prognosis of patients. An analysis of prognostic factors for overall survival identified diameter of the tumor (<3.0 cm), absence of major portal vein invasion, absence of distant metastasis, Union Internationale Contre Le Cancer tumor lymph node metastasis stage (I or II), neutrophil lymphocytic ratio (<2.1) and the frequency of MDSCs (<30.5 %) as factors that prolonged overall survival time after HAIC. Even in the group adjusted with progressive levels of tumors, patients with a low frequency of MDSCs had a significantly longer overall survival time. In conclusion, the frequency of MDSCs before the treatment is a prognostic factor in HAIC against HCC.

摘要

肝动脉灌注化疗(HAIC)已被用作晚期肝细胞癌(HCC)患者索拉非尼的替代治疗方法。在本研究中,我们对接受HAIC治疗的晚期HCC患者的各种免疫细胞反应进行了比较分析,包括肿瘤相关抗原(TAA)特异性T细胞、调节性T细胞(Tregs)和骨髓来源的抑制细胞(MDSCs)。该研究共检查了36例HCC患者。采用干扰素γ酶联免疫斑点试验检测TAA特异性T细胞的频率。通过多色荧光激活细胞分选分析检测Tregs和MDSCs的频率。使用干扰素(IFN)/5-氟尿嘧啶(FU)或IFN/FU +顺铂进行的HAIC治疗调节了各种免疫细胞的频率。在22.2%的患者中,HAIC后TAA特异性T细胞的频率增加。虽然HAIC后Tregs的频率降低,但这与患者的预后无关。对总生存预后因素的分析确定,肿瘤直径(<3.0 cm)、无主要门静脉侵犯、无远处转移、国际抗癌联盟肿瘤淋巴结转移分期(I或II)、中性粒细胞淋巴细胞比率(<2.1)和MDSCs频率(<30.5%)是HAIC后延长总生存时间的因素。即使在根据肿瘤进展程度进行调整的组中,MDSCs频率低的患者总生存时间也显著更长。总之,治疗前MDSCs的频率是HAIC治疗HCC的一个预后因素。