CD4^(+)T细胞中CD4^(+)Treg比例与早期非小细胞肺癌患者隐匿性淋巴结转移关系  

Relationship between CD4^(+)Treg ratio in CD4^(+)T cells and occult lymph node metastasis in early non-small cell lung cancer patients

作　　者：胡梦钰 景洪标 李超卓 杨丽颖 孙晓蓉 邢力刚 HU Mengyu;JING Hongbiao;LI Chaozhuo;YANG Liying;SUN Xiaorong;XING Ligang(Graduate School,Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan,Shandong 250117,China;Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan,Shandong 250117,China;School of Clinical Medicine,Shandong Second Medical University,Weifang,Shandong 261000,China;Shandong University Cheeloo College of Medicine,Jinan.Shandong 250100,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)研究生院,山东济南250117 [2]山东省肿瘤防治研究院,山东省肿瘤医院放疗科,山东第一医科大学(山东省医学科学院),山东济南250117 [3]山东省肿瘤防治研究院,山东省肿瘤医院病理科,山东第一医科大学(山东省医学科学院),山东济南250117 [4]山东省肿瘤防治研究院,山东省肿瘤医院核医学科,山东第一医科大学(山东省医学科学院),山东济南250117 [5]山东第二医科大学临床医学院,山东潍坊261000 [6]山东大学齐鲁医学院,山东济南250100

出　　处：《中华肿瘤防治杂志》2024年第22期1378-1384,共7页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金面上项目(82172866,82373424);山东省自然科学基金重点支持项目(ZR2021LZL005);山东省科学技术厅纵向项目(2021CXGC011102)。

摘　　要：目的探讨非小细胞肺癌(NSCLC)肿瘤中心(TC)和侵袭性边缘(IM)区域中CD4^(+)T细胞、CD4^(+)Treg细胞密度以及CD4^(+)Treg/CD4^(+)T与临床隐匿性淋巴结转移(OLNM)发生的关系。方法回顾性收集2016-01-01-2021-12-31山东省肿瘤医院接受肺癌根治术的150例临床T_(1~2)期的早期NSCLC患者术后标本,构建包含TC和IM区域的组织芯片(TMA),并采用多色免疫荧光技术对CD4、Foxp3和CK进行染色。根据患者影像学和病理学淋巴结转移情况,将患者分成无淋巴结转移组(cN^(-)pN^(-)组,n=79)和隐匿性淋巴结转移组(cN^(-)pN^(+)组,n=71)。使用中位数确定截断值,将患者分为高/低密度组,高/低比值组,通过二元logistic分析发生OLNM的关键因素。结果IM区域中,与cN-pN-组相比,cN^(-)pN^(+)组中CD4^(+)T细胞密度高(65.52 vs 81.07,Z=-2.242,P=0.025)。单因素分析表明,肿瘤CT直径>3 cm(OR=3.54,95%CI为1.30~9.64,P=0.013)、TC区域高CD4^(+)Treg/CD4^(+)T(OR=2.23,95%CI为1.16~4.30,P=0.016)、IM区域高CD4^(+)T密度(OR=2.23,95%CI为1.16~4.30,P=0.016)和IM区域高CD4^(+)Treg/CD4^(+)T(OR=2.52,95%CI为1.31~4.87,P=0.006)均是早期NSCLC患者发生OLNM的危险因素。多因素logistic分析表明,肿瘤CT直径>3 cm(OR=3.10,95%CI为1.16~8.26,P=0.024)和IM区域中高CD4^(+)Treg/CD4^(+)T比值(OR=2.58,95%CI为1.32~5.05,P=0.006)是早期NSCLC患者发生OLNM的危险因素。结论NSCLC患者IM区域中CD4^(+)Treg/CD4^(+)T比值增加可能抑制肿瘤免疫,增加临床OLNM发生的风险。Objective To investigate the relationship between the densities of CD4^(+)T cells,CD4^(+)Treg cells,and the pro-portion of CD4^(+)Treg to CD4^(+)T cells in the tumor center(TC)and invasive margin(IM)regions of non-small cell lung cancer(NSCLC)and the occurrence of clinically occult lymph node metastasis(OLNM).Methods Postoperative speci-mens of 150 early-stage NSCLC patients with clinical stages T_(1)to T_(2)who underwent radical lung cancer surgery at Shandong Cancer Hospital from January 1,2016 to December 31,2021 were retrospectively collected,and tissue microar-rays(TMAs)containing TC and IM regions were constructed,and CD4/Foxp3/CK/DAPI were stained by using multicol-or immunofluorescence technology staining.According to the imaging and pathological lymph node metastasis status of the patients,they were divided into a group without lymph node metastasis(cN^(-)pN^(-)group,n=79)and a group with occult lymph node metastasis(cN^(-)pN^(+)group,n=71).The median was used to determine the cutoff value,and the pa-tients were divided into high/low density group,high/low ratio group,and the key factors for the occurrence of OLNM were analyzed by binary logistic analysis.Results In the IM region,compared with the cN^(-)pN^(-)group,the cN^(-)pN^(+)group had a higher density of CD4^(+)T cells(65.52 vs 81.07,Z=-2.242,P=0.025).Univariate analysis showed that tumor CT diameter>3 cm(OR=3.54,95%CI:1.30-9.64,P=0.013),high CD4^(+)Treg/CD4^(+)T in the TC region(OR=2.23,95%CI:1.16-4.30,P=0.016),high CD4^(+)T density in the IM region(OR=2.23,95%CI:1.16-4.30,P=0.016),and high CD4^(+)Treg/CD4^(+)T in the IM region(OR=2.52,95%CI:1.31-4.87,P=0.006)were risk fac-tors for OLNM in early-stage NSCLC patients.Multivariate logistic analysis showed that tumor CT diameter>3 cm(OR=3.10,95%CI:1.16-8.26,P=0.024)and high CD4^(+)Treg/CD4^(+)T ratio in the IM area(OR=2.58,95%CI:1.32-5.05,P=0.006)were risk factors for OLNM in early-stage NSCLC patients.Conclusion Increased NSCLC CD4^(+)Treg/CD4^(+)T ratio may suppress tumor immunity and increase the

关 键 词：非小细胞肺癌 临床隐匿性淋巴结转移 肿瘤免疫微环境 CD4^(+)T CD4^(+)Treg 

分 类 号：R734.2[医药卫生—肿瘤]