[1]张涵,祖育娜,张华.非小细胞肺癌患者肺泡灌洗液中T淋巴细胞亚群及血清炎症因子与免疫检查点抑制剂相关性肺炎的关系[J].新乡医学院学报,2023,40(9):824-828.[doi:10.7683/xxyxyxb.2023.09.004]
 ZHANG Han,ZU Yuna,ZHANG Hua.Correlations of T lymphocyte subsets in bronchoalveolar lavage fluid and serum inflammatory factors with immune checkpoint inhibitor-associated pneumonia in patients with non-small cell lung cancer[J].Journal of Xinxiang Medical University,2023,40(9):824-828.[doi:10.7683/xxyxyxb.2023.09.004]
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非小细胞肺癌患者肺泡灌洗液中T淋巴细胞亚群及血清炎症因子与免疫检查点抑制剂相关性肺炎的关系
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
40卷
期数:
2023年9
页码:
824-828
栏目:
临床研究
出版日期:
2023-09-05

文章信息/Info

Title:
Correlations of T lymphocyte subsets in bronchoalveolar lavage fluid and serum inflammatory factors with immune checkpoint inhibitor-associated pneumonia in patients with non-small cell lung cancer
作者:
张涵12祖育娜2张华2
(1.新乡医学院,河南 新乡 453003;2.郑州大学附属郑州中心医院呼吸重症医学科,河南 郑州 450002)
Author(s):
ZHANG Han12ZU Yuna2ZHANG Hua2
(1.Xinxiang Medical University,Xinxiang 453003,Henan Province,China;2.Department of Respiratory and Critical Care Medicine,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450002,Henan Province,China)
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
Keywords:
non-small cell lung cancerimmune checkpoint inhibitor-associated pneumoniainflammatory factorsT lymphocyte subsets
分类号:
R734.2
DOI:
10.7683/xxyxyxb.2023.09.004
文献标志码:
A
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-10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-10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-10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-10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-10水平异常,CD4+/CD8+、IL-6、IL-8、IL-10等指标可能有助于临床评估ICIP严重程度。
Abstract:
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 stage Ⅳ of 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.

参考文献/References:

[1] YONG J,HUANG L,CHEN G,et al.High expression of Stabilin-2 predicts poor prognosis in non-small-cell lung cancer[J].Bioengineered,2021,12(1):3426-3433.
[2] HSU M L,NAIDOO J.Principles of immunotherapy in non-small cell lung cancer[J].Thorac Surg Clin,2020,30(2):187-198.
[3] PATEL S A,WEISS J.Advances in the treatment of non-small cell lung cancer:immunotherapy[J].Clin Chest Med,2020,41(2):237-247.
[4] BODOR J N,BOUMBER Y,BORGHAEI H.Biomarkers for immune checkpoint inhibition in non-small cell lung cancer(NSCLC)[J].Cancer,2020,126(2):260-270.
[5] BRUECKL W M,FICKER J H,ZEITLER G.Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC)[J].BMC Cancer,2020,20(1):1185-1193.
[6] LIN X,DENG H,YANG Y,et al.Peripheral blood biomarkers for early diagnosis,severity,and prognosis of checkpoint inhibitor-related pneumonitis in patients with lung cancer[J].Front Oncol,2021,11(7):8832-8839.
[7] CHU X,ZHAO J,ZHOU J,et al.Association of baseline peripheral-blood eosinophil count with immune checkpoint inhibitor-related pneumonitis and clinical outcomes in patients with non-small cell lung cancer receiving immune checkpoint inhibitors[J].Lung Cancer,2020,150(12):76-82.
[8] 王旋,崔立春,党升强.非小细胞肺癌放化疗联合靶向治疗对血清肿瘤标志物、免疫功能及Cyclin D3水平影响的相关研究[J].现代检验医学杂志,2021,36(4):25-30.
WANG X,CUI L C,DANG S Q.Effects of radiotherapy and chemotherapy combined with targeted therapy on serum tumor markers,immune function and CyclinD3 level in non-small cell lung cancer[J].J Mod Lab Med,2021,36(4):25-30.
[9] KAUFFMANN-GUERRERO D,KAHNERT K,KIEFL R,et al.Systemic inflammation and pro-inflammatory cytokine profile predict response to checkpoint inhibitor treatment in NSCLC:a prospective study[J].Sci Rep,2021,11(1):10919-10926.
[10] ETTINGER D S,AKERLEY W,BORGHAEI H,et al.Non-small cell lung cancer,version 2.2013[J].J Natl Compr Canc Netw,2013,11(6):645-653.
[11] 中华医学会呼吸病学分会肺癌学组.免疫检查点抑制剂相关肺炎诊治专家共识[J].中华结核和呼吸杂志,2019,42(11):820-825.
LUNG CANCER GROUP,RESPIRATORY DISEASE BRANCH,CHINESE MEDICAL ASSOCIATION.Expert consensus on the diagnosis and treatment of pneumonia associated with immune checkpoint inhibitors[J].Chin J Tubercul Resp,2019,42(11):820-825.
[12] CHAO Y,ZHOU J,HSU S,et al.Risk factors for immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer[J].Transl Lung Cancer Res,2022,11(2):295-306.
[13] LEE P H,YANG T Y,CHEN K C,et al.Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors[J].Sci Rep,2021,11(1):9381-9387.
[14] JRGENSEN N,HVIID T V F,NIELSEN L B,et al.Tumour-infiltrating CD4-,CD8- and FOXP3-positive immune cells as predictive markers of mortality in BRCA1- and BRCA2-associated breast cancer[J].Br J Cancer,2021,125(10):1388-1398.
[15] 黎海燕,扶红根,丁国标,等.山莨菪碱联合布地奈德对肺炎感染患儿肺功能和免疫功能及细胞因子的影响[J].中华医院感染学杂志,2020,30(20):3174-3179.
LI H Y,FU H G,DING G B,et al.Effects of anisodamine combined with budesonide on pulmonary function,immune function and cytokines in children with pneumonia infection[J].Chin J Nosocomiol,2020,30(20):3174-3179.
[16] 张消,司小敏,焦婉,等.经皮125I植入联合化疗在中晚期非小细胞肺癌治疗中的应用及对CD3+、CD4+、CD8+、CD4+/CD8+的影响[J].中国现代医学杂志,2021,31(13):35-39.
ZHANG X,SI X M,JIAO W,et al.Application of percutaneous radioactive iodine 125 particle implantation combined with chemotherapy in treatment of advanced non-small cell lung cancer and its effects on CD3+,CD4+,CD8+,and CD4+/CD8+[J].Chin J Mod Med,2021,31(13):35-39.
[17] LIU Y,GAO Y,LIN T.Expression of interleukin-1 (IL-1),IL-6,and tumor necrosis factor-α (TNF-α) in non-small cell lung cancer and its relationship with the occurrence and prognosis of cancer pain[J].Ann Palliat Med,2021,10(12):12759-12766.
[18] KANG D H,PARK C K,CHUNG C,et al.Baseline serum interleukin-6 levels predict the response of patients with advanced non-small cell lung cancer to PD-1/PD-L1 inhibitors[J].Immun Netw,2020,20(3):e27.
[19] JO H,YOSHIDA T,HORINOUCHI H,et al.Prognostic significance of cachexia in advanced non-small cell lung cancer patients treated with pembrolizumab[J].Cancer Immunol Immunother,2022,71(2):387-398.
[20] 段新如,汪修平,王爱民.血清肿瘤标志物检测在非小细胞肺癌侵袭和转移中的意义[J].中国肿瘤临床与康复,2020,27(3):335-338.
DUAN X R,WANG X P,WANG A M.Significance of detection of serum tumor markers in tumor invasion and metastasis of non-small cell lung cancer[J].Chin J Clin Oncol Rehabil,2020,27(3):335-338.
[21] WANG H,ZHOU F,ZHAO C,et al.Interleukin-10 is a promising marker for immune-related adverse events in patients with non-small cell lung cancer receiving immunotherapy[J].Front Immunol,2022,13(2):313-320.
[22] 席宝宇,张红娟,张妮,等.姑息化疗对晚期肺癌患者细胞免疫功能及相关炎症因子水平的影响及护理对策[J].中国肿瘤临床与康复,2020,27(2):243-246.
XI B Y,ZHANG H J,ZHANG N,et al.Effect of palliative chemotherapy on cellular immune function and related inflammatory factors in patients with advanced lung cancer and nursing strategies[J].Chin J Clin Oncol Rehabil,2020,27(2):243-246.

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更新日期/Last Update: 2023-09-05