非小细胞肺癌患者肿瘤微环境中TAMs及PD-1表达水平及与临床预后的关系

摘要
图/表
参考文献(20)
相关文章 (15)

全文: PDF (0 KB) HTML (42 KB)
输出: BibTeX | EndNote (RIS)

摘要目的探讨肿瘤相关巨噬细胞（TAMs）及程序性死亡受体1（PD-1）在非小细胞肺癌（NSCLC）患者肿瘤微环境中的表达及其与患者预后的关系。方法选取2019年1月至12月于九江市第一人民医院胸外科初次确诊且择期手术的76例NSCLC患者作为研究对象，均于术中采集癌组织和癌旁组织，通过免疫组化分析TAMs表型和PD-1表达水平，收集患者临床预后因素，观察1年生存率，分析不同临床预后因素下TAMs表型和PD-1表达水平分布特征，采用COX回归分析患者1年内死亡的风险因素。结果NSCLC患者癌组织PD-1、CD206阳性表达高于癌旁组织，CD86阳性表达低于癌旁组织，差异有统计学意义（P＜0.05）。癌组织PD-1和CD206阳性表达成正相关（P＜0.05）。腺癌PD-1阳性表达水平高于鳞癌，差异有统计学意义（P＜0.05）。高分化CD86表达水平高于低分化和中分化，差异有统计学意义（P＜0.05）；高分化和中分化CD206表达水平低于低分化，差异有统计学意义（P＜0.05）。临床Ⅲ期和Ⅱ期PD-1阳性表达水平高于Ⅰ期，差异有统计学意义（P＜0.05）；临床Ⅲ期和Ⅱ期CD86阳性表达水平低于Ⅰ期，差异有统计学意义（P＜0.05）。浸润性生长患者的CD206表达水平高于非浸润性生长，差异有统计学意义（P＜0.05）。76 例 NSCLC 患者 1年生存率为76.32%；PD-1（β=0.031，RR=1.031，95%CI=1.007～1.056）和CD206（β=0.066，RR=1.068，95%CI=1.013～1.127）是 NSCLC 患者 1 年生存率的危险因素（P＜0.05）。结论 NSCLC 癌组织及癌旁组织中PD-1、CD86和CD206的表达存在明显差异，PD-1高表达、M2型巨噬细胞的高浸润特性可明显增加患者1年内死亡率。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	张佳秀
	邓林锋
	石建邦
	吴健卫

关键词 ：非小细胞肺癌, 微环境, 程序性死亡受体1, CD86, CD206, 表达, 预后

Abstract：Objective To investigate the expression of tumor-associated macrophages (TAMs)and programmed death receptor-1(PD-1)in the tumor microenvironment of patients with non-small cell lung cancer(NSCLC)and their relationship with the prognosis of patients.Methods A total of 76 patients with NSCLC who were diagnosed for the first time in the Department of Thoracic Surgery of the First People′s Hospital of Jiujiang City from January 2019 to December and were undergoing elective surgery were selected as the research objects.The cancer tissues and adjacent tissues were collected during the operation,and the TAMs phenotype and PD-1 expression level were analyzed by immunohistochemistry,the clinical prognostic factors of the patients were collected,the 1-year survival rate was observed,and the TAMs phenotype and PD-1 expression level distribution characteristics under different clinical prognostic factors were analyzed.COX regression were used to analysis the risk factors of patients′death within 1 year.Results The positive expression of PD-1 and CD206 in NSCLC were higher than those in the adjacent tissues,and the positive expression of CD86 was lower than that of the adjacent tissues,and the differences were statistically significant (P<0.05).The positive expression of PD-1 and CD206 in cancer tissues was positively correlated (P＜0.05).The positive expression level of PD-1 in adenocarcinoma was higher than that of squamous cell carcinoma,and the difference was statistically significant(P<0.05).The expression level of well-differentiated CD86 was higher than that of poorly differentiated and moderately differentiated,and the difference was statistically significant(P<0.05).The expression of well-differentiated and moderately differentiated CD206 were lower than that of low-differentiation differentiation,and the differences were statistically significant(P<0.05).The positive expression level of PD-1 in clinical stage Ⅲ and Ⅱ were higher than that in stage Ⅰ,and the differencs were statistically significant(P<0.05).The positive expression level of CD86 in clinical stage Ⅲ and Ⅱ were lower than that in stage Ⅰ,and the differences were statistically significant(P<0.05).The expression level of CD206 in patients with invasive growth was higher than that in non-invasive growth,and the difference was statistically significant(P<0.05).The 1-year survival rate of 76 NSCLC patients was 76.32%.PD-1(β=0.031,RR=1.031,95%CI=1.007-1.056)and CD206(β=0.066,RR=1.068,95%CI=1.013-1.127)were risk factors for the 1-year survival rate of NSCLC patients(P<0.05).Conclusion The expressions of PD-1,CD86 and CD206 in NSCLC cancer tissues and adjacent tissues are significantly different.The high expression of PD-1 and the high infiltration characteristics of M2 macrophages can significantly increase the mortality of patients within one year.

Key words： Non-small cell lung cancer Microenvironment Programmed death receptor-1 CD86 CD206 Expression Prognosis

基金资助:江西省卫生健康委科技计划项目（SKJP2202012 42）。

作者简介: 张佳秀（1988-），女，安徽宿松人，硕士，研究方向：肺癌。

引用本文:

张佳秀；邓林锋；石建邦；吴健卫. 非小细胞肺癌患者肿瘤微环境中TAMs及PD-1表达水平及与临床预后的关系[J]. 中国当代医药, 2021, 28(32): 4-8.
ZHANG Jia-xiu；DENG Lin-feng；SHI Jian-bang；WU Jian-wei. Expression levels of TAMs and PD-1 in the tumor microenvironment of patients with non-small cell lung cancer and their relationship with clinical prognosis. 中国当代医药, 2021, 28(32): 4-8.

链接本文:

http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2021/V28/I32/4

[1]	中国肺癌筛查与早诊早治指南制定顾问组，中国肺癌筛查与早诊早治指南制定专家组，中国肺癌筛查与早诊早治指南制定工作组.中国肺癌筛查与早诊早治指南（2021，北京）[J].中华肿瘤杂志，2021，43（3）：243-268.
[3]	张强，吴邵雅，张靖.放疗对肿瘤微环境的重塑及增强免疫治疗疗效机制的研究进展[J].肿瘤防治研究，2021，48（1）：1-6.
[4]	杨万里，任欢.组织定居巨噬细胞在肿瘤微环境中的作用[J].国际免疫学杂志，2021，44（1）：86-90.
[5]	朱奎璇，官杰.程序性死亡蛋白-1/程序性死亡蛋白受体-1在临床疾病中的研究进展[J].中国当代医药，2020，27（15）：40-43.
[6]	张用，毕建平，皮国良，等.国际肺癌研究协会第八版国际肺癌 TNM 分期修订稿解读[J].肿瘤防治研究，2016，43（4）：313-318.
[7]	冯婷婷，陈众众，闫文锦，等.基于SEER数据库的肿瘤直径大于7.0厘米的非小细胞肺癌患者预后分析[J].肿瘤防治研究，2021，48（1）：49-54.
[8]	Schütz F，Stefanovic S，Mayer L，et al.PD-1/PD-L1 Pathway in Breast Cancer[J].Oncol Res Treat，2017，40（5）：294-297.
[9]	Neubert NJ，Schmittnaegel M，Bordry N，et al.T cell-induced CSF1 promotes melanoma resistance to PD1 blockade[J].Sci Transl Med，2018，10（436）：eaan3311.
[10]	Zhu J，Armstrong AJ，Friedlander TW，et al.Biomarkers of immunotherapy in urothelial and renal cell carcinoma：PDL1，tumor mutational burden，and beyond[J].J Immunother Cancer，2018，6（1）：4.
[11]	李浩洋，秦娜，俞孟军，等.PD-L1高表达晚期非小细胞肺癌患者单纯免疫治疗与免疫联合化疗疗效比较[J].中国肺癌杂志，2021，24（3）：161-166.
[12]	弓瑾，李建强.PD-1/PD-L1抑制剂在非小细胞肺癌治疗中的应用进展[J].中国当代医药，2018，25（9）：29-32.
[13]	刘晔，洪润丹，王志国，等.人单核细胞和外周血单个核细胞衍生的巨噬细胞极化特性的比较[J].国际口腔医学杂志，2020，47（3）：286-292.
[14]	田广招，杨振，查康康，等.脱细胞软骨基质对巨噬细胞极化的调控[J].中国组织工程研究，2021，25（22）：3545-3550.
[15]	刘怡辰，向卉楠，诸君，等.肿瘤相关巨噬细胞在肿瘤中作用的研究进展[J].肿瘤研究与临床，2021，33（2）：149-153.
[16]	赵昆，时荣臣，缪洪明.肿瘤相关巨噬细胞的脂质代谢重编程[J].四川大学学报（医学版），2021，52（1）：45-49.
[17]	Rahal OM，Wolfe AR，Mandal PK，et al.Blocking Interleukin （IL）4-and IL13-Mediated Phosphorylation of STAT6 （Tyr641）Decreases M2 Polarization of Macrophages and Protects Against Macrophage-Mediated Radioresistance of Inflammatory Breast Cancer[J].Int J Radiat Oncol Biol Phys，2018，100（4）：1034-1043.
[18]	Armand P，Nagler A，Weller EA，et al.Disabling immune tolerance by programmed death-1 blockade with pidilizumab after au-tologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma：results of an international phase Ⅱ trial[J].Clin Onco1，2013，31（33）：4199-4206.
[2]	尹志芳，林鲜，郭甲.Ⅳ期非小细胞肺癌化疗同期三维放疗后不同生存状态变化对患者近期疗效、远期生存率及不良反应的影响[J].临床和实验医学杂志，2021，20（3）：266-269.
[19]	Lin H，Wei S，Hurt EM，et al.Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression[J].J Clin Invest，2018，128（2）：805-815.
[20]	Jeon S，Rowe AM，Carroll KL，et al.PD-L1/B7-H1 Inhibits Viral Clearance by Macrophages in HSV-1-Infected Corneas[J].J Immunol，2018，200（11）：3711-3719.