Programmed death ligand 1 expression and CD8+ tumor-infiltrating lymphocyte density differences between paired primary and brain metastatic lesions in non-small cell lung cancer
Programmed death ligand 1 expression and CD8+ tumor-infiltrating lymphocyte density differences between paired primary and brain metastatic lesions in non-small cell lung cancer
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DOI：
10.1016/j.bbrc.2018.03.053
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发表时间：
2018-04-15
影响因子：
3.1
通讯作者：
Zhu, Bo
中科院分区：
文献类型：
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作者：
Zhou, Jie;Gong, Zhihua;Zhu, Bo
靶向程序性细胞死亡-1/程序性死亡配体1（PD-L1）通路的免疫治疗在非小细胞肺癌（NSCLC）患者的脑转移（BM）中显示出有希望的抗肿瘤活性，具有可接受的安全性特征;然而，原发性病变和颅内病变的缓解率通常不同。研究是必要的，以确定响应生物标志物的详细表征。在这项研究中，我们的目的是比较PD-1/PD-L1阻断的两个主要缓解生物标志物PD-L1表达和CD 8（+）肿瘤浸润淋巴细胞（TIL）密度在晚期NSCLC中配对原发灶和脑转移灶之间的差异。我们观察到，在原发性病变或BM中，只有少数患者在肿瘤细胞和肿瘤浸润免疫细胞上具有共同的PD-L1表达。此外，我们发现BM中CD 8（+）TIL的数量明显少于原发性肺癌。与高基质CD 8（+）TIL计数相比，BM中低基质CD 8（+）TIL计数与显著较短的总生存期相关。值得注意的是，我们证明了原发性肺癌及其相应BM之间PD-L1表达和CD 8（+）TIL密度的差异。这种异质性与BM发生的时间显著相关。我们的研究强调了抗PD-1/13 D-L1治疗生物标志物的时空异质性，这在临床实践中应予以关注。(C)2018爱思唯尔公司All rights reserved.
Immunotherapy targeting the programmed cell death-1/programmed death ligand 1 (PD-L1) pathway has shown promising antitumor activity in brain metastases (BMs) of non-small cell lung cancer (NSCLC) patients with an acceptable safety profile; however, the response rates often differ between primary lesions and intracranial lesions. Studies are necessary to identify detailed characterizations of the response biomarkers. In this study, we aimed to compare the differences of PD-L1 expression and CD8(+) tumor-infiltrating lymphocyte (TIL) density, two major response biomarkers of PD-1/PD-L1 blockade, between paired primary and brain metastatic lesions in advanced NSCLC. We observed that among primary lesions or BMs, only a small number of patients harbored common PD-L1 expression on both tumor cells and tumor-infiltrating immune cells. Additionally, we found that the numbers of CD8(+) TILs were significantly fewer in BMs than in primary lung cancers. Low stromal CD8(+) TIL numbers in BMs were associated with significantly shorter overall survival compared to high stromal CD8(+) TIL counts. Notably, we demonstrated a discrepancy in PD-Ll expression and CD8(+) TIL density between primary lung cancers and their corresponding BMs. Such heterogeneities are significantly associated with the time at which BMs occurred. Our study emphasizes the spatial and temporal heterogeneity of biomarkers for anti-PD-1/13D-L1 therapy, which should be concerned in clinical practice. (C) 2018 Elsevier Inc. All rights reserved.