PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes
PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes
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DOI：
10.1093/annonc/mdv192
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发表时间：
2015-07-01
影响因子：
50.5
通讯作者：
Caldas, C.
中科院分区：
文献类型：
--
作者：
Ali, H. R.;Glont, S. -E.;Caldas, C.
背景资料：程序性死亡配体1（PD-L1）在实体瘤中的表达已被证明可以预测患者是否可能对抗PD-L1治疗有反应。为了评估PD-L1抑制在乳腺癌中的治疗潜力，我们评估了大量乳腺肿瘤中PD-L1蛋白表达的患病率和意义。患者和方法：在METABRIC基因组研究招募的418名患者的肿瘤中评价了CD 274（PD-L1）拷贝数、转录本和蛋白质水平之间的相关性。免疫组织化学用于检测组织微阵列中乳腺肿瘤中的PD-L1蛋白，这些组织微阵列来自招募到基于人群的研究（N = 4079）和NEAT随机对照试验（N = 1684）的5763名患者。结果：PD-L1蛋白数据可用于来自ESTA和NEAT研究的可能的5763个肿瘤中的3916个。在6%（235/ 3916）的肿瘤中观察到免疫细胞表达PD-L1，仅在1.7%（66/ 3916）中观察到肿瘤细胞表达。PD-L1在基底细胞样肿瘤中表达最多.这在通过组合拷贝数和表达谱对肿瘤进行亚型分型的情况下都观察到[IntClust 10 i. e.基底样肿瘤为PD-L1免疫细胞阳性; P < 0.001]，并且其中使用基于替代IHC的分类器[ 19%（56/ 302）的基底样肿瘤为PD-L1免疫细胞阳性; P < 0.001]。此外，在5个肿瘤中观察到CD 274（PD-L1）扩增，其中4个为IntClust 10。肿瘤细胞或浸润性免疫细胞的PD-L1表达与细胞毒性T细胞和调节性T细胞的浸润呈正相关（P < 0.001）。在ER阴性疾病中，PD-L1与疾病特异性生存率改善之间存在名义上显著的相关性（风险比0.53，95%置信区间0.26- 1.07; P = 0.08）。结论：PD-L1在乳腺癌中的表达是罕见的，在基底样肿瘤中明显富集，并与浸润淋巴细胞相关。PD-L1抑制可能使19%的基底细胞样肿瘤患者受益，其中蛋白质表达。
Background: Expression of programmed death ligand 1 ( PD- L1) in solid tumours has been shown to predict whether patients are likely to respond to anti- PD- L1 therapies. To estimate the therapeutic potential of PD- L1 inhibition in breast cancer, we evaluated the prevalence and significance of PD- L1 protein expression in a large collection of breast tumours. Patients and methods: Correlations between CD274 ( PD- L1) copy number, transcript and protein levels were evaluated in tumours from 418 patients recruited to the METABRIC genomic study. Immunohistochemistry was used to detect PD- L1 protein in breast tumours in tissue microarrays from 5763 patients recruited to the SEARCH population- based study ( N = 4079) and the NEAT randomised, controlled trial ( N = 1684). Results: PD- L1 protein data was available for 3916 of the possible 5763 tumours from the SEARCH and NEAT studies. PD- L1 expression by immune cells was observed in 6% ( 235/ 3916) of tumours and expression by tumour cells was observed in just 1.7% ( 66/ 3916). PD- L1 was most frequently expressed in basal- like tumours. This was observed both where tumours were subtyped by combined copy number and expression profiling [ 39% ( 17/ 44) of IntClust 10 i. e. basallike tumours were PD- L1 immune cell positive; P < 0.001] and where a surrogate IHC- based classifier was used [ 19% ( 56/ 302) of basal- like tumours were PD- L1 immune cell positive; P < 0.001]. Moreover, CD274 ( PD- L1) amplification was observed in five tumours of which four were IntClust 10. Expression of PD- L1 by either tumour cells or infiltrating immune cells was positively correlated with infiltration by both cytotoxic and regulatory T cells ( P < 0.001). There was a nominally significant association between PD- L1 and improved disease- specific survival ( hazard ratio 0.53, 95% confidence interval 0.26- 1.07; P = 0.08) in ER- negative disease. Conclusions: Expression of PD- L1 is rare in breast cancer, markedly enriched in basal- like tumours and is correlated with infiltrating lymphocytes. PD- L1 inhibition may benefit the 19% of patients with basal- like tumours in which the protein is expressed.