胸腺肽α1缓解EGFR-TKI对EGFR敏感突变NSCLC患者T淋巴细胞亚群抑制的研究
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摘要
目的探讨表皮生长因子受体(EGFR)敏感突变非小细胞肺癌(NSCLC)患者接受EGFR-TKI单药,以及EGFR-TKI联合胸腺肽α1治疗前后外周血T淋巴细胞亚群的变化。方法采集我院2008年5月至2018年8月期间接受单药EGFR-TKI和EGFR-TKI联合胸腺肽α1治疗的NSCLC患者的外周血T淋巴细胞亚群数据。结果在患者EGFR-TKI耐药前,患者接受EGFR-TKI单药治疗后外周血CD4+T淋巴细胞,CD8+T淋巴细胞,CD3+T淋巴细胞数量较接受EGFR-TKI单药治疗之前显著降低(P<0.05);患者接受EGFR-TKI联合胸腺肽α1治疗后外周血CD4+T淋巴细胞,CD8+T淋巴细胞,CD3+T淋巴细胞数量与EGFR-TKI单药治疗前相比稍降低,但无统计学差异(P> 0.05)。结论胸腺肽α1在某种程度上可以缓解EGFR-TKI对EGFR突变NSCLC患者外周血T淋巴细胞亚群的抑制。
Objective Comparative analysis of peripheral blood T lymphocyte subsets before patients treated with epidermal growth factor receptor tyrosine kinase inhibitor( EGFR-TKI) and patients after receiving EGFR-TKI monotherapy or combined with Thymosin α1 therapy. Methods The data of peripheral blood T lymphocyte subsets of patients receiving EGFR-TKI and EGFR-TKI combined with Thymosin α1 was collected from May 2008 to August 2018. Results The number of Peripheral blood CD4+,CD8+and CD3+T lymphocyte of patients were decreased after EGFR-TKI treatment alone( P < 0. 05),the number of those T lymphocytes shown no difference before EGFR-TKI monotherapy and after receiving EGFR-TKI plus Thymosin α1 therapy( P> 0.05). Conclusions EGFR-TKI could decrease the peripheral blood T lymphocyte subsets of patients treated with EGFR-TKI,thymosin α1 was able to reverse the inhibitory effect of EGFR-TKI on peripheral blood T lymphocyte subsets of patients to some extent.
Objective Comparative analysis of peripheral blood T lymphocyte subsets before patients treated with epidermal growth factor receptor tyrosine kinase inhibitor( EGFR-TKI) and patients after receiving EGFR-TKI monotherapy or combined with Thymosin α1 therapy. Methods The data of peripheral blood T lymphocyte subsets of patients receiving EGFR-TKI and EGFR-TKI combined with Thymosin α1 was collected from May 2008 to August 2018. Results The number of Peripheral blood CD4+,CD8+and CD3+T lymphocyte of patients were decreased after EGFR-TKI treatment alone( P < 0. 05),the number of those T lymphocytes shown no difference before EGFR-TKI monotherapy and after receiving EGFR-TKI plus Thymosin α1 therapy( P> 0.05). Conclusions EGFR-TKI could decrease the peripheral blood T lymphocyte subsets of patients treated with EGFR-TKI,thymosin α1 was able to reverse the inhibitory effect of EGFR-TKI on peripheral blood T lymphocyte subsets of patients to some extent.
引文
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8 Han JY,Park K,Kim SW,et al.First-SIGNAL:first-line singleagent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung[J].J Clin Oncol,2012,30(10):1122-1128.
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10 Luo Q,Gu Y,Zheng W,et al.Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c-Raf/ERK cascade and Akt signaling pathway[J].Toxicol Appl Pharmacol,2011,251(2):130-136.
11 Danielli R,Cisternino F,Giannarelli D,et al.Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1:investigating immune checkpoints synergy[J].Expert Opin Biol Ther,2018,18(sup1):77-83.
12 Garaci E,Pica F,Matteucci C,et al.Historical review on thymosin alpha1 in oncology:preclinical and clinical experiences[J].Expert Opin Biol Ther,2015,15 Suppl 1:S31-S39.
13 Jiang J,Wang X,Tian J,et al.Thymosin plus cisplatin with vinorelbine or gemcitabine for non-small cell lung cancer:A systematic review and meta-analysis of randomized controlled trials[J].Thorac Cancer,2011,2(4):213-220.
14余荣,孙宇,蔡庆,等.α1胸腺肽减轻放射性肺损伤[J].中国肺癌杂志,2011,14(3):187-193.
15 Moody TW,Fagarasan M,Zia F,et al.Thymosin alpha 1 downregulates the growth of human non-small cell lung cancer cells in vitro and in vivo[J].Cancer Res,1993,53(21):5214-5218.
16 Garaci E,Pica F,Serafino A,et al.Thymosin alpha1 and cancer:action on immune effector and tumor target cells[J].Ann N Y Acad Sci,2012,1269:26-33.
17 Wee P,Wang Z.Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways[J].Cancers(Basel),2017,9(5).
18 Li M,Ong SS,Rajwa B,et al.The SH3 domain of Lck modulates T-cell receptor-dependent activation of extracellular signal-regulated kinase through activation of Raf-1[J].Mol Cell Biol,2008,28(2):630-641.
19 Roskoski RJ.Erb B/HER protein-tyrosine kinases:Structures and small molecule inhibitors[J].Pharmacol Res,2014,87:42-59.
20 Knutsen AP,Freeman JJ,Mueller KR,et al.Thymosin-alpha1 stimulates maturation of CD34+stem cells into CD3+4+cells in an in vitro thymic epithelia organ coculture model[J].Int J Immunopharmacol,1999,21(1):15-26.
21 Romani L,Bistoni F,Gaziano R,et al.Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling[J].Blood,2004,103(11):4232-4239.
22 Jennings RN,Grayson JM,Barton ES.Type I interferon signaling enhances CD8+T cell effector function and differentiation during murine gammaherpesvirus 68 infection[J].J Virol,2014,88(24):14040-14049.
2 Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
3 Herbst RS,Heymach JV,Lippman SM.Lung cancer[J].N Engl JMed,2008,359(13):1367-1380.
4 Allemani C,Weir HK,Carreira H,et al.Global surveillance of cancer survival 1995-2009:analysis of individual data for 25,676,887patients from 279 population-based registries in 67 countries(CONCORD-2)[J].Lancet,2015,385(9972):977-1010.
5 Rosell R,Carcereny E,Gervais R,et al.Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer(EURTAC):a multicentre,open-label,randomised phase 3 trial[J].Lancet Oncol,2012,13(3):239-246.
6 Watanabe S,Inoue A,Nukiwa T,et al.Comparison of Gefitinib Versus Chemotherapy in Patients with Non-small Cell Lung Cancer with Exon 19 Deletion[J].Anticancer Res,2015,35(12):6957-6961.
7 Zhou C,Wu YL,Chen G,et al.Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutationpositive non-small-cell lung cancer(OPTIMAL,CTONG-0802):a multicentre,open-label,randomised,phase 3 study[J].Lancet Oncol,2011,12(8):735-742.
8 Han JY,Park K,Kim SW,et al.First-SIGNAL:first-line singleagent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung[J].J Clin Oncol,2012,30(10):1122-1128.
9 de Visser KE,Eichten A,Coussens LM.Paradoxical roles of the immune system during cancer development[J].Nat Rev Cancer,2006,6(1):24-37.
10 Luo Q,Gu Y,Zheng W,et al.Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c-Raf/ERK cascade and Akt signaling pathway[J].Toxicol Appl Pharmacol,2011,251(2):130-136.
11 Danielli R,Cisternino F,Giannarelli D,et al.Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1:investigating immune checkpoints synergy[J].Expert Opin Biol Ther,2018,18(sup1):77-83.
12 Garaci E,Pica F,Matteucci C,et al.Historical review on thymosin alpha1 in oncology:preclinical and clinical experiences[J].Expert Opin Biol Ther,2015,15 Suppl 1:S31-S39.
13 Jiang J,Wang X,Tian J,et al.Thymosin plus cisplatin with vinorelbine or gemcitabine for non-small cell lung cancer:A systematic review and meta-analysis of randomized controlled trials[J].Thorac Cancer,2011,2(4):213-220.
14余荣,孙宇,蔡庆,等.α1胸腺肽减轻放射性肺损伤[J].中国肺癌杂志,2011,14(3):187-193.
15 Moody TW,Fagarasan M,Zia F,et al.Thymosin alpha 1 downregulates the growth of human non-small cell lung cancer cells in vitro and in vivo[J].Cancer Res,1993,53(21):5214-5218.
16 Garaci E,Pica F,Serafino A,et al.Thymosin alpha1 and cancer:action on immune effector and tumor target cells[J].Ann N Y Acad Sci,2012,1269:26-33.
17 Wee P,Wang Z.Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways[J].Cancers(Basel),2017,9(5).
18 Li M,Ong SS,Rajwa B,et al.The SH3 domain of Lck modulates T-cell receptor-dependent activation of extracellular signal-regulated kinase through activation of Raf-1[J].Mol Cell Biol,2008,28(2):630-641.
19 Roskoski RJ.Erb B/HER protein-tyrosine kinases:Structures and small molecule inhibitors[J].Pharmacol Res,2014,87:42-59.
20 Knutsen AP,Freeman JJ,Mueller KR,et al.Thymosin-alpha1 stimulates maturation of CD34+stem cells into CD3+4+cells in an in vitro thymic epithelia organ coculture model[J].Int J Immunopharmacol,1999,21(1):15-26.
21 Romani L,Bistoni F,Gaziano R,et al.Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling[J].Blood,2004,103(11):4232-4239.
22 Jennings RN,Grayson JM,Barton ES.Type I interferon signaling enhances CD8+T cell effector function and differentiation during murine gammaherpesvirus 68 infection[J].J Virol,2014,88(24):14040-14049.