PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC).
PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC).
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DOI：
10.18632/oncotarget.15839
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发表时间：
2017-04-18
期刊：
影响因子：
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通讯作者：
Gu Y
中科院分区：
文献类型：
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作者：
Jiang L;Su X;Zhang T;Yin X;Zhang M;Fu H;Han H;Sun Y;Dong L;Qian J;Xu Y;Fu X;Gavine PR;Zhou Y;Tian K;Huang J;Shen D;Jiang H;Yao Y;Han B;Gu Y
为了探索可能从抗PD-1/PD-L1单药或联合治疗中获益的潜在患者人群，本研究旨在分析NSCLC中的一组免疫治疗相关生物标志物（PD-1、PD-L1、CTLA-4和CD 8）和靶向治疗生物标志物（EGFR、KRAS、ALK、ROS 1和MET）。采用免疫组化、免疫荧光、测序和荧光原位杂交技术对297例NSCLC患者的肿瘤标本进行分析，其中腺癌（AD）156例，鳞癌（SCC）129例。43.1%的NSCLC患者肿瘤细胞（TC）PD-L1染色阳性率≥ 5%。此外，双色免疫荧光显示，大多数PD-L1/CD 8双阳性肿瘤浸润淋巴细胞（TIL）已浸润到肿瘤核心。最后，所有八种生物标志物的联合分析显示，在26%的SCC和76%的AD样本中，肿瘤PD-L1阳性与NSCLC致癌肿瘤驱动因子的已知改变重叠。我们对八种生物标志物重叠的说明为使用抗PD-1/PD-L1免疫疗法（作为单一药物或与靶向疗法联合）的个性化治疗策略提供了对非小细胞肺癌的直观概述。我们还首次报道了PD-L1和CD 8双阳性TIL主要位于肿瘤核心内。
In order to explore the potential patient population who could benefit from anti PD-1/PD-L1 mono or combination therapies, this study aimed to profile a panel of immunotherapy related biomarkers (PD-1, PD-L1, CTLA-4 and CD8) and targeted therapy biomarkers (EGFR, KRAS, ALK, ROS1 and MET) in NSCLC. Tumor samples from 297 NSCLC patients, including 156 adenocarcinomas (AD) and 129 squamous cell carcinomas (SCC), were analyzed using immunohistochemistry, immunofluorescence, sequencing and fluorescence in situ hybridization. 43.1% of NSCLC patients had PD-L1 positive staining on ≥ 5% tumor cells (TC). Furthermore, dual color immunofluorescence revealed that the majority of PD-L1/CD8 dual positive tumor infiltrating lymphocytes (TIL) had infiltrated into the tumor core. Finally, combined analysis of all eight biomarkers showed that tumor PD-L1 positivity overlapped with known alterations in NSCLC oncogenic tumor drivers in 26% of SCC and 76% of AD samples. Our illustration of the eight biomarkers’ overlap provides an intuitive overview of NSCLC for personalized therapeutic strategies using anti-PD-1/PD-L1 immune therapies, either as single agents, or in combination with targeted therapies. For the first time, we also report that PD-L1 and CD8 dual positive TILs are predominantly located within the tumor core.