肿瘤浸润淋巴细胞
医学
CD8型
肺癌
雷达51
免疫组织化学
癌症研究
肿瘤科
免疫疗法
川地68
CD3型
内科学
病理
癌症
DNA修复
免疫系统
免疫学
生物
基因
生物化学
作者
Mariam Gachechiladze,J Škarda,Daniela Skanderová,Ivo Überall,Vı́tězslav Kolek,Petra Smičková,Petr Vojta,Jana Vbrková,Marián Hajdúch,Ilay Shani,Zdeněk Kolář,Rolf A. Stahel,Walter Weder,Undīne Rulle,Alex Soltermann,Markus Joerger
出处
期刊:Lung Cancer
[Elsevier]
日期:2020-09-01
卷期号:147: 30-38
被引量:12
标识
DOI:10.1016/j.lungcan.2020.06.025
摘要
DNA repair proteins have emerged as potential predictors for immunotherapy response alongside PD-L1 expression, tumor-infiltrating lymphocytes (TILs) and tumor mutational burden. We analyzed expression of PD-L1, TILs count and expression of the homologous recombination (HR) protein RAD51, as potential prognostic factors in patients with resected non-small-cell lung carcinoma (NSCLC).Discovery set included 96 NSCLC patients from the University Hospital Olomouc (Czech Republic) and a replication set included 1109 NSCLC patients from University Hospital Zurich (Switzerland). Tissue microarrays (TMAs) were stained using the automated staining platform Ventana Benchmark Ultra with antibodies against RAD51,CD3, CD8, CD68 and PD-L1.Loss of nuclear RAD51 protein was associated with high TILs (r=-0.25, p = 0.01) and PD-L1 status (10.6 vs. 2.4 %, p = 0.012) in patients receiving neoadjuvant chemo-/radiotherapy (CT/RT). In silico analysis from the TCGA data set showed a negative relationship between RAD51 mRNA expression and CD45 (r = ‒0.422, p < 0.0001), CD68 (r = ‒0.326, p < 0.001), CD3 (r = ‒0.266, p < 0.001) and CD8 (r = ‒0.102, p < 0.001). RAD51 low/PD-L1 high patients were clustered as separate entity in the replication set and in TCGA dataset. High TILs status was significantly associated with improved OS in the replication set (unadjusted HR = 0.57, 95 % CI 0.42-0.76, p < 0.001). Similar results have been seen for CD3, CD8 and CD68.In conclusion, RAD51 nuclear loss is weakly associated with increased TILs and high PD-L1 at the time of surgery in curatively resected NSCLC and after prior exposure to neoadjuvant chemo- or radiotherapy. Both high TILs and RAD51 nuclear loss were confirmed as independent prognostic factors in curatively resected NSCLC.
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