摘要
目的探讨肺泡灌洗液(BALF)中T淋巴细胞亚群及血清炎症因子与非小细胞肺癌(NSCLC)患者并发免疫检查点抑制剂(ICI)相关性肺炎(ICIP)的关系。方法选择2018年1月至2022年4月郑州市中心医院收治的经过免疫治疗的60例NSCLC患者为研究对象,根据患者是否发生ICIP分为ICIP组和无ICIP组,每组30例。另根据ICIP严重程度将ICIP组患者分为1~2级组(n=21)和3~4级组(n=9)。收集所有患者的慢性阻塞性肺疾病(COPD)病史、吸烟史、肿瘤组织学类型、临床分期、突变状态、治疗方案、ICI类型、美国东部肿瘤协作组行为状态(ECOG PS)评分等资料;检测所有患者BALF中T淋巴细胞亚群CD3^(+)、CD4^(+)、CD8^(+)水平,并计算CD4^(+)/CD8^(+);采集所有患者纳入研究24 h内的外周静脉血,检测血清中白细胞介素(IL)-6、IL-8、IL^(-1)0水平。采用Spearman法分析BALF中T淋巴细胞亚群及血清炎症因子水平与ICIP严重程度的关系。结果ICIP组与无ICIP组患者的年龄、性别、COPD病史、吸烟史、肿瘤组织学类型、临床分期、突变状态、治疗方案、ICI类型、ECOG PS评分比较差异无统计学意义(P>0.05)。ICIP组NSCLC临床Ⅳ期患者占比显著高于无ICIP组(P<0.05)。ICIP组患者BALF中CD4^(+)、CD4^(+)/CD8^(+)水平显著低于无ICIP组,CD3^(+)、CD8^(+)水平显著高于无ICIP组(P<0.05)。ICIP组患者血清中IL-6、IL-8、IL^(-1)0水平显著高于无ICIP组(P<0.05)。3~4级组ICIP患者BALF中CD4^(+)、CD4^(+)/CD8^(+)水平显著低于1~2级组(P<0.05),BALF中CD3^(+)、CD8^(+)水平及血清中IL-6、IL-8、IL^(-1)0水平显著高于1~2级组(P<0.05)。ICIP严重程度与CD4^(+)/CD8^(+)呈负相关(r=-0.567,P<0.05),与血清IL-6、IL-8、IL^(-1)0水平呈正相关(r=0.426、0.478、0.390,P<0.05)。结论NSCLC并发ICIP患者存在T淋巴细胞亚群CD4^(+)、CD3^(+)、CD4^(+)/CD8^(+)、CD8^(+)及炎症因子IL-6、IL-8、IL^(-1)0水平异常,CD4^(+)/CD8^(+)、IL-6、IL-8、IL^(-1)0等指标可能有助于临床评估ICIP严重程度。
Objective To investigate the correlations of T lymphocyte subsets in bronchoalveolar lavage fluid(BALF)and serum inflammatory factors with immune checkpoint inhibitor(ICI)-associated pneumonia(ICIP)in patients with non-small cell lung cancer(NSCLC).Methods Sixty NSCLC patients who underwent immunotherapy in the Zhengzhou Central Hospital from January 2018 to April 2022 were selected as the study subjects,and the patients were divided into the ICIP group and the non-ICIP group according to whether they developed ICIP,with 30 cases in each group.The patients in the ICIP group were also divided into the grade 1-2 group(n=21)and the grade 3-4 group(n=9)according to the severity of ICIP.Chronic obstructive pulmonary disease(COPD)history,smoking history,tumour histological type,clinical stage,mutation status,treatment plan,ICI type,Eastern Cooperative Oncology Group performance status(ECOG PS)score of all patients were collected.The CD3^(+),CD4^(+)and CD8^(+)levels of T lymphocyte subsets in the BALF of all patients were detected and CD4^(+)/CD8^(+)was calculated;the peripheral venous blood from all patients within 24 hours of after inclusion in this study was collected,and the serum IL-6,IL-8 and IL-10 levels were detected.The relationship between T lymphocyte subsets in BALF,serum inflammatory factor levels and the severity of ICIP patients was analyzed by Spearman method.Results There was no statistically significant difference in age,gender,history of COPD,smoking history,histological type of tumour,clinical stage,mutation status,treatment plan,ICI type,and ECOG PS scores between the ICIP group and non-ICIP group(P>0.05).The percentage of patients with clinical stageⅣof NSCLC in the ICIP group was significantly higher than that in the non-ICIP group(P<0.05).The levels of CD4^(+),CD4^(+)/CD8^(+)in BALF of patients in the ICIP group were significantly lower than those in the non-ICIP group(P<0.05),and the levels of CD3^(+)and CD8^(+)were significantly higher than those in the non-ICIP group(P<0.05).The serum IL-6,IL-8 and IL-10 levels of patients in the ICIP group were significantly higher than those in the non-ICIP group(P<0.05).The levels of CD4^(+)and CD4^(+)/CD8^(+)in the BALF of patients in the grade 3-4 group were significantly lower than those in the grade 1-2 group(P<0.05),and the levels of CD3^(+)and CD8^(+)in BALF and serum IL-6,IL-8 and IL-10 levels were significantly higher than those in the grade 1-2 group(P<0.05).The severity of ICIP was negatively correlated with CD4^(+)/CD8^(+)(r=-0.567,P<0.05),and it was positively correlated with serum IL-6,IL-8 and IL-10 levels(r=0.426,0.478,0.390;P<0.05).Conclusion The levels of T lymphocyte subsets CD4^(+),CD3^(+),CD4^(+)/CD8^(+),CD8^(+)and inflammatory factors IL-6,IL-8 and IL-10 are abnormal in NSCLC complicated with ICIP patients,and the indexes of CD4^(+)/CD8^(+),IL-6,IL-8 and IL-10 may be helpful in clinical assessment of the severity of ICIP.
作者
张涵
祖育娜
张华
ZHANG Han;ZU Yuna;ZHANG Hua(Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Department of Respiratory and Critical Care Medicine,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450002,Henan Province,China)
出处
《新乡医学院学报》
CAS
2023年第9期824-828,共5页
Journal of Xinxiang Medical University
基金
河南省医学科技攻关计划项目(编号:LHGJ20210777)。
关键词
非小细胞肺癌
免疫检查点抑制剂相关性肺炎
炎症因子
T淋巴细胞亚群
non-small cell lung cancer
immune checkpoint inhibitor-associated pneumonia
inflammatory factors
T lymphocyte subsets
