中国肺癌杂志2024,Vol.27Issue(12):903-910,8.DOI:10.3779/j.issn.1009-3419.2024.102.46
TIM3+CD8+T细胞在非小细胞肺癌中心区和非中心区微环境中的表达及其临床意义
TIM3+CD8+T Cell Expression and Clinical Significance in the Central and Non-central Tumor Microenvironment of Non-small Cell Lung Cancer
摘要
Abstract
Background and objective One of the most important treatment modalities for non-small cell lung cancer(NSCLC)is immune checkpoint inhibitor.Nevertheless,a small percentage of patients do not respond well to these therapies,highlighting the significance of identifying important CD8+T cell subsets for immunotherapy and creating trust-worthy biomarkers.The purpose of this study is to assess the potential utility of TIM3+CD8+T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment.Methods Based on biopsy techniques,tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions.Using flow cytometry,the infiltration of TIM3+CD8+T cells and the surface expression of programmed cell death 1(PD-1)on these cells were examined,and their correlations with the effectiveness of immunotherapy were assessed.Results The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+T lymphocytes compared to the non-central region(P<0.0001).This pattern was found in both subgroups with tumor diameters≥3 cm or<3 cm(P<0.01).In comparison to TIM3-CD8+T cells,TIM3+CD8+T cells showed higher levels of PD-1(P<0.001),with more PD-1+TIM3+CD8+T cells invading the non-central region(P<0.01).Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+T cells in the tumor non-central region compared to non-responders,with lower levels correlated with better clinical outcomes(P<0.01),while no correlation was identified in the tumor central region(P>0.05).According to reciever operating characteristic(ROC)curve analysis,TIM3+CD8+T cells in the tumor non-central region had an area under the curve(AUC)of 0.9375 for predicting the effectiveness of immunotherapy,which was considerably higher than that of TIM3+CD8+T cells in the tumor central region and programmed cell death ligand 1(PD-L1)[tumor proportion score(TPS)].Conclusion In the tumor microenvironment of NSCLC,TIM3+CD8+T cells show regional distribution patterns.The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.关键词
肺肿瘤/TIM3/PD-1/CD8+T细胞/肿瘤微环境/免疫治疗Key words
Lung neoplasms/TIM3/PD-1/CD8+T cells/Tumor microenvironment/Immunotherapy引用本文复制引用
吴家娟,郭诗樱,吕蕾蕾,翟家为,沈宇,陈成,瞿秋霞..TIM3+CD8+T细胞在非小细胞肺癌中心区和非中心区微环境中的表达及其临床意义[J].中国肺癌杂志,2024,27(12):903-910,8.基金项目
本研究受苏州市科教强卫重点项目(No.ZDXM2024002)资助 This study was supported by the grant from Key Project of Science,Education and Health Strengthening in Suzhou(No.ZDXM2024002)(to Cheng CHEN). (No.ZDXM2024002)