TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune cells in head and neck squamous cell carcinoma.
TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune cells in head and neck squamous cell carcinoma.
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DOI：
10.1136/esmoopen-2017-000257
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发表时间：
2018
期刊：
影响因子：
7.3
通讯作者：
Postel-Vinay S
中科院分区：
文献类型：
--
作者：
Leduc C;Adam J;Louvet E;Sourisseau T;Dorvault N;Bernard M;Maingot E;Faivre L;Cassin-Kuo MS;Boissier E;Dessoliers MC;Robin A;Casiraghi O;Even C;Temam S;Olaussen KA;Soria JC;Postel-Vinay S
抗程序性细胞死亡-1/程序性细胞死亡配体1(PD-1/PD-L1)疗法在晚期头颈部鳞状细胞癌(HNSCC)中显示出良好的疗效，在非选择人群中的总有效率约为20%，并对生存有利。诱导多西紫杉醇、铂和氟尿嘧啶(TPF)是否改变PD-L1的表达或肿瘤免疫浸润物尚不清楚。对2006-2013年间在法国维勒朱伊夫的Gustave Roussy接受TPF诱导和手术治疗的局部晚期HNSCC患者进行了回顾性研究。配对样本(TPF前和TPF后)的患者被保留以供进一步分析。PD-L1的表达通过免疫组织化学方法进行定量。本研究的目的是比较PD-L1在肿瘤细胞(TC)和免疫细胞(IC)(≥阳性阈值为5%)上的表达。并测定TPF前后CD8+、Foxp3+淋巴细胞密度。在接受诱导TPF的313名患者中，86名接受了手术；其中21名患者获得了配对样本。TC和IC中分别有2个和5个样本的基线PD-L1表达为≥5%。诱导化疗后PD-L1表达显著增加，诱导化疗后IC阳性15例(71%)，TC阳性8例(38%)(P=0.005；Wilcoxon秩和检验)。肿瘤浸润性CD8+平均密度也显著增加(P=0.01)。两组间Foxp3+表达、CD8/Foxp3比值及预后无显著差异。TPF诱导化疗可增加肿瘤浸润性IC的PD-L1阳性表达，以及CD8+淋巴细胞 密度。这些结果需要在更大的数据集上进行独立验证，并可能有助于晚期HNSCC的治疗策略。
Antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) therapies have demonstrated promising activity in advanced head and neck squamous cell carcinoma (HNSCC), with overall response rates of approximately 20% in unselected populations and survival benefit. Whether induction docetaxel, platinum and fluorouracil (TPF) modifies PD-L1 expression or tumour immune infiltrates is unknown. Patients with locally advanced HNSCC treated at Gustave Roussy (Villejuif, France) between 2006 and 2013 by induction TPF followed by surgery were retrospectively considered. Patients with paired samples (pre-TPF and post-TPF) were kept for further analysis. PD-L1 expression was quantified by immunohistochemistry according to a validated protocol. The objective of the study was to compare PD-L1 expression on tumour cells (TC) and immune cells (IC) (positivity threshold of ≥5%) before and after TPF. CD8+ and Foxp3+ lymphocytes densities before and after TPF were also quantified. Out of 313 patients receiving induction TPF, 86 underwent surgery; paired samples were available for 21 of them. Baseline PD-L1 expression was ≥5% in two and five samples for TC and IC, respectively. A significant increase of PD-L1 expression was observed after TPF, with 15 samples (71%) presenting a positive staining in IC after induction chemotherapy (P=0.003; Wilcoxon rank-sum test) and eight samples (38%) in TC (P=0.005; Wilcoxon rank-sum test). Tumour-infiltrating CD8+ mean densities also significantly increased post-TPF (P=0.01). There was no significant difference in Foxp3+ expression, CD8/Foxp3 ratio or correlation with outcome. TPF induction chemotherapy in advanced HNSCC increases PD-L1 positivity on tumour-infiltrating ICs, as well as CD8+ lymphocytes density. These results warrant independent validation on larger datasets and might help therapeutic strategy in advanced HNSCC.
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期刊：
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DOI：
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发表时间：
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期刊：
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