食管鳞状细胞癌患者外周血和肿瘤组织来源的髓源抑制性细胞中PD-1和TIM-3的表达
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摘要
目的:探讨程序性细胞死亡蛋白-1(PD-1)和T细胞免疫球蛋白黏蛋白-3(TIM-3)在食管鳞状细胞癌(ESCC)患者外周血和肿瘤组织来源的髓源抑制性细胞(MDSCs)上的表达情况。方法:将48例ESCC手术患者外周血单个核细胞和肿瘤组织单细胞进行CD11b、CD14、CD33、HLA-DR标记,并检测单核MDSCs和多形核MDSCs两个亚群上PD-1和TIM-3的表达,分析其表达水平与临床病理指标的关系。结果:肿瘤组织来源的MDSCs上PD-1和TIM-3的表达均高于外周血来源的MDSCs(P <0. 05)。肿瘤组织来源的多形核MDSCs上PD-1和TIM-3的表达水平高于单核MDSCs(P <0. 05),但是PD-1、TIM-3高表达和低表达患者生存曲线差异无统计学意义(P>0. 05)。PD-1、TIM-3在外周血和肿瘤组织来源的MDSCs上的表达均与ESCC患者临床病理指标无关(P> 0. 05)。结论:PD-1和TIM-3在ESCC患者肿瘤组织来源的MDSCs上的表达明显升高,二者可能成为与MDSCs功能相关的标志物。
Aim: To investigate the expressions of PD-1 and TIM-3 on myeloid-derived suppressor cells(MDSCs) derived from peripheral blood and tumor tissue in patients with esophageal squamous cell carcinoma(ESCC). Methods: Peripheral blood mononuclear cells and tumor tissue derived single cells of 48 patients with ESCC were labelled with monoclonal antibodies,and the expressions of PD-1 and TIM-3 on the two subtypes of MDSCs were detected by flow cytometry.The association between the expression levels of PD-1 and TIM-3 and clinicopathological parameters was analyzed. Results:The expressions of PD-1 and TIM-3 on tumor tissue-derived MDSCs were significantly higher than those on peripheral bloodderived MDSCs(P < 0. 05). There were significant differences in the expressions of PD-1 and TIM-3 between tumor-derived PMN-MDSCs and M-MDSCs(P < 0. 05). However,there was no significant difference in survival between patients with high expressions of PD-1 and TIM-3 and those with low expressions(P > 0. 05). There was higher expression of PD-1 on peripheral blood-derived M-MDSCs of males than that of females(P < 0. 05). The expressions of PD-1 and TIM-3 on tumorand peripheral blood-derived MDSCs were not associated with clinicopathological parameters of ESCC patients(P > 0. 05).Conclusion: The expressions of PD-1 and TIM-3 significantly increase in tumor tissue-derived MDSCs from ESCC patients,and PD-1 and TIM-3 may become new markers to identify MDSCs.
Aim: To investigate the expressions of PD-1 and TIM-3 on myeloid-derived suppressor cells(MDSCs) derived from peripheral blood and tumor tissue in patients with esophageal squamous cell carcinoma(ESCC). Methods: Peripheral blood mononuclear cells and tumor tissue derived single cells of 48 patients with ESCC were labelled with monoclonal antibodies,and the expressions of PD-1 and TIM-3 on the two subtypes of MDSCs were detected by flow cytometry.The association between the expression levels of PD-1 and TIM-3 and clinicopathological parameters was analyzed. Results:The expressions of PD-1 and TIM-3 on tumor tissue-derived MDSCs were significantly higher than those on peripheral bloodderived MDSCs(P < 0. 05). There were significant differences in the expressions of PD-1 and TIM-3 between tumor-derived PMN-MDSCs and M-MDSCs(P < 0. 05). However,there was no significant difference in survival between patients with high expressions of PD-1 and TIM-3 and those with low expressions(P > 0. 05). There was higher expression of PD-1 on peripheral blood-derived M-MDSCs of males than that of females(P < 0. 05). The expressions of PD-1 and TIM-3 on tumorand peripheral blood-derived MDSCs were not associated with clinicopathological parameters of ESCC patients(P > 0. 05).Conclusion: The expressions of PD-1 and TIM-3 significantly increase in tumor tissue-derived MDSCs from ESCC patients,and PD-1 and TIM-3 may become new markers to identify MDSCs.
引文
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[2]连晶瑶,李红,黄岚,等.体外扩增人脐带血来源的NK细胞对食管癌细胞的促凋亡作用[J].中国肿瘤生物治疗杂志,2017,24(2):117
[3]TOPALIAN SL,TAUBE JM,ANDERS RA,et al.Mechanismdriven biomarkers to guide immune checkpoint blockade in cancer therapy[J].Nat Rev Cancer,2016,16(5):275
[4]张毅,刘艳粉.嵌合抗原受体T细胞治疗实体瘤的现状和挑战[J].郑州大学学报(医学版),2018,53(6):701
[5]QUAIL DF,JOYCE JA.Microenvironmental regulation of tumor progression and metastasis[J].Nat Med,2013,19(11):1423
[6]POPOVIC A,JAFFEE EM,ZAIDI N.Emerging strategies for combination checkpoint modulators in cancer immunotherapy[J].J Clin Invest,2018,128(8):3209
[7]QIN GH,LIAN JY,HUANG L,et al.Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis[J].Oncoimmunology,2018,7(7):1
[8]CHEN L.Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity[J].Nat Rev Immunol,2004,4(5):336
[9]DAS M,ZHU C,KUCHROO VK.Tim-3 and its role in regulating anti-tumor immunity[J].Immunol Rev,2017,276(1):97
[10]NAM S,LEE A,LIM J,et al.Analysis of the expression and regulation of PD-1 protein on the surface of myeloid-derived suppressor cells(MDSCs)[J].Biomol Ther(Seoul),2019,27(1):63
[11]NAKAMURA K,KASSEM S,CLEYNEN A,et al.Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment[J].Cancer Cell,2018,33(4):634
[12]LI PP,CHEN XF,QIN GH,et al.Maelstrom directs myeloid-derived suppressor cells to promote esophageal squamous cell carcinoma progression via activation of the Akt1/Rel A/IL8 signaling pathway[J].Cancer Immunol Res,2018,6(10):1246
[13]SONG MJ,CHEN XF,WANG LP,et al.Future of anti-PD-1/PD-L1 applications:combinations with other therapeutic regimens[J].Chin J Cancer Res,2018,30(2):157
[14]DUFFY A,ZHAO F,HAILE L,et al.Comparative analysis of monocytic and granulocytic myeloid-derived suppressor cell subsets in patients with gastrointestinal malignancies[J].Cancer Immunol Immunother,2013,62(2):299