中国肺癌杂志2025，Vol.28Issue(8)：576-584,9.DOI:10.3779/j.issn.1009-3419.2025.102.30
CAFs-TAECs空间距离预测肺鳞状细胞癌新辅助化免病理缓解
Prediction of Spatial Distance of CAFs-TAECs for Pathological Response to Neoadjuvant Chemoimmunotherapy in Lung Squamous Cell Carcinoma
摘要
Abstract
Background and objective Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer(NSCLC).However,lung squamous cell carcinoma(SCC)generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma(ADC).The aim of this study is to elucidate how baseline cancer-associated fibroblasts(CAFs)and tumor-associated endothelial cells(TAECs)influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC.Methods We retrospectively collected pretreatment biopsy samples from 104 patients with stage Ⅱ-Ⅲ NSCLC who underwent neoadjuvant chemotherapy(NAC)or neoadjuvant chemoimmunotherapy(NAIC)at Shandong Cancer Hospital between January 1,2018 and December 31,2023.Tissue micro-arrays were constructed using an automated arrayer,and multiplex immunofluorescence staining(α-SMA/CD31/CK/DAPI)was performed to identify CAFs(α-SMA+/CK)and TAECs(CD31+/CK).Quantitative analyses included CAFs and TAECs densities,the nearest neighbor distance(NND)between CAFs and TAECs,and their spatial proximity(30 μm).Differences in major pathological response(MPR)between groups,defined as residual viable tumor cells ≤10％in resected specimens after neoadjuvant therapy,were assessed using thex2test.The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators,and receiver operating characteristic(ROC)curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort.Results Among the 104 NSCLC patients who received neoadjuvant therapy,35 underwent NAIC and 69 received NAC.Overall,patients with SCC were more likely to achieve MPR compared with those with ADC(50.0％vs 22.4％,P=0.006).This trend persisted in the NAIC subgroup(72.7％vs 30.8％,P=0.038),whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup.At base-line,prior to NAIC or NAC,programmed cell death ligand 1(PD-L1)/programmed cell death 1(PD-1)expression,CAFs and TAECs densities,CAFs-TAECs NND,and CAFs-TAECs proximity(30 μm)showed no significant differences between SCC and ADC.In patients with SCC receiving NAIC,baseline PD-L1/PD-1 expression,CAFs density,and TAECs density showed not significant differences between MPR and NMPR groups.However,the CAFs-TAECs distance was significantly greater in the MPR group(NND:31.2 vs 24.7 μm,P=0.038),and the number of TAECs within 30 μm of CAFs was significantly lower(proximity:1.1 vs 3.6,P=0.038).Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC(OR=36.00,95％CI:2.68-1486.88,P=0.019).Furthermore,ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity(30 μm)exhibited strong predictive performance for MPR in SCC patients treated with NAIC,with an area under the curve(AUC)of 0.893,sensitivity of 0.857,and specificity of 1.000.Conclusion CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC,which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.关键词
肺肿瘤/新辅助治疗/癌症相关成纤维细胞/肿瘤相关血管内皮细胞Key words
Lung neoplasms/Neoadjuvant therapy/Cancer-associated fibroblasts/Tumor-associated endothelial cells引用本文复制引用
叶笃明,杨丽颖,赵亦民,文印会,赵苗青,邢力刚,孙晓蓉..CAFs-TAECs空间距离预测肺鳞状细胞癌新辅助化免病理缓解[J].中国肺癌杂志,2025,28(8):576-584,9.基金项目
本研究受国家自然科学基金项目(No.82373424、No.82172866)、四大慢病国家科技重大专项(No.2024ZD0525900)、山东省科学技术厅纵向项目(No.2021CXGC011102)、山东省重点研发计划项目(No.2024CXPT084)及山东省肿瘤医院学科集群创新工程(No.GF002)资助 This study was supported by the grants from the National Natural Science Foundation of China(No.82373424,to Xiaorong SUN （No.82373424、No.82172866）
No.82172866,to Ligang XING),the Noncommunicable Chronic Diseases-National Science and Tech-nology Major Project(No.2024ZD0525900,to Ligang XING),the Department of Science & Technology of Shandong Province(No.2021CXGC011102,to Ligang XING),the Key Research and Development Program of Shandong Province(No.2024CXPT084,to Jian ZHU)and Collaborative Academic Innovation Project of Shandong Cancer Hospital(No.GF002,to Ligang XING). （No.2024ZD0525900,to Ligang XING）
