[1]武晓雷,钟志祝,孟敏敏,等.基于程序性死亡配体1表达与肿瘤浸润淋巴细胞的非小细胞肺癌免疫治疗疗效预测及机制探讨[J].陕西医学杂志,2026,(4):555-560.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.022]
　WU Xiaolei,ZHONG Zhizhu,MENG Minmin,et al.Prediction of immunotherapy efficacy in nonsmall cell lung cancer based on PDL1 expression and tumorinfiltrating lymphocytes:A mechanistic study[J].,2026,(4):555-560.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.022]
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基于程序性死亡配体1表达与肿瘤浸润淋巴细胞的非小细胞肺癌免疫治疗疗效预测及机制探讨

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年4期
页码:
555-560
栏目:
临床病理
出版日期:
2026-04-05

文章信息/Info

Title:
Prediction of immunotherapy efficacy in nonsmall cell lung cancer based on PDL1 expression and tumorinfiltrating lymphocytes:A mechanistic study
作者:
武晓雷1; 钟志祝1; 孟敏敏1; 单壮壮1; 陈迎亚1; 朱宏2; 刘丹阳1
（1.南京中医药大学沭阳附属医院病理科，江苏 宿迁 223600;2.南京医科大学第一附属医院消化内科，江苏 南京210029）
Author(s):
WU Xiaolei1; ZHONG Zhizhu1; MENG Minmin1; SHAN Zhuangzhuang1; CHEN Yingya1; ZHU Hong2; LIU Danyang1
（1.Department of Pathology,Shuyang Affiliated Hospital of Nanjing University of Chinese Medicine,Suqian 223600,China；2.Department of Gastroenterology,The First Affiliated Hospital with Nanjing Medical University,Nanjing 210029,China）
关键词:
非小细胞肺癌; 程序性死亡配体1; 肿瘤浸润淋巴细胞; 免疫检查点抑制剂; Janus激酶/信号传导和转录激活因子信号通路; 肿瘤免疫微环境
Keywords:
Nonsmall cell lung cancer; Programmed deathligand 1; Tumorinfiltrating lymphocytes; Immune checkpoint inhibitors; JAK/STAT signaling pathway; Tumor immune microenvironment
分类号:
R 734.2
DOI:
DOI:10.3969/j.issn.1000-7377.2026.04.022
文献标志码:
A
摘要:
目的：探讨程序性死亡配体1（PDL1）表达与肿瘤浸润淋巴细胞（TILs）在非小细胞肺癌（NSCLC）患者免疫治疗中的协同预测价值，并阐明其在干扰素γ（IFNγ）诱导下的分子调控机制。方法：回顾性纳入接受免疫检查点抑制剂（ICIs）治疗的40例晚期NSCLC患者，评估肿瘤组织中PDL1表达水平及TILs浸润程度，并根据TILs浸润程度高、低分组，比较各组的临床疗效。采用Cox比例风险模型分析影响无进展生存期（PFS）和总体生存（OS）的因素。在基础实验中，使用A549细胞模型，分别给予不同浓度的IFNγ刺激并干预Janus激酶（JAK）抑制剂Ruxolitinib，通过qPCR、Western blot和流式细胞术检测PDL1表达变化，探讨JAK/信号传导和转录激活因子（STAT）通路在PDL1上调中的作用。结果：Cox回归模型中，TILs高低与PFS的HR为4.275（95%CI：1.350~13.540），PDL1表达与PFS的HR为0.923（95%CI：0.881~0.967）；TILs高低与OS的HR为25.17（95%CI：4821~131.405），PDL1表达与OS的HR为0.928（95%CI：0.882~0.977）。IFNγ显著诱导A549细胞PDL1的mRNA及蛋白水平呈剂量依赖性上升（P<0.001），而Ruxolitinib显著抑制该效应（P<0.01）。结论：TILs与PDL1的联合评估能够更准确预测NSCLC患者对免疫治疗的疗效与预后，其上调机制通过IFNγJAK/STAT通路调控，为免疫治疗的精准分层与靶向干预提供了理论依据。
Abstract:
Objective:To investigate the synergistic predictive value of programmed cell death ligand 1 (PDL1) expression and tumorinfiltrating lymphocytes (TILs) in immune therapy for nonsmall cell lung cancer (NSCLC) patients,and to elucidate their molecular regulatory mechanisms under interferonγ (IFNγ) induction.Methods：A retrospective analysis was conducted on 40 advanced NSCLC patients who received immune checkpoint inhibitors (ICIs).The expression levels of PDL1 and TILs infiltration in tumor tissues were assessed,and patients were grouped based on the degree of TILs infiltration.The clinical efficacy of each group was compared.The Cox proportional hazard model was used to analyze the factors influencing progressionfree survival (PFS) and overall survival (OS).In the basic experiments,A549 cells were treated with varying concentrations of IFNγ and the JAK inhibitor Ruxolitinib,and changes in PDL1 expression were measured by qPCR,Western blot,and flow cytometry.The role of the JAK/STAT pathway in the upregulation of PDL1 was explored.Results:Clinical analysis showed that in the Cox regression model,TILs high vs.low had an HR of 4.275 (95%CI:1.350~13.540),and PDL1 expression had an HR of 0.923 (95%CI:0.881~0.967) for PFS;for OS,TILs high vs.low had an HR of 25.17 (95%CI:4.821~131.405),and PDL1 expression had an HR of 0.928 (95%CI:0.882~0.977).Mechanistic studies showed that IFNγ significantly induced a dosedependent increase in PDL1 mRNA and protein levels in A549 cells (P<0.001),while Ruxolitinib significantly inhibited this effect (P<0.01).Conclusion:The combined evaluation of TILs and PDL1 can more accurately predict the efficacy and prognosis of immune therapy in NSCLC patients.The upregulation mechanism is regulated via the IFNγJAK/STAT pathway,providing a theoretical basis for the precise stratification and targeted intervention in immune therapy.

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备注/Memo

备注/Memo:
江苏省干部保健科研课题（BJ2401）
更新日期/Last Update: 2026-04-05