Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Pathology, University of Cambridge, Cambridge
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge.
Ann Oncol. 2015 Jul;26(7):1488-93. doi: 10.1093/annonc/mdv192. Epub 2015 Apr 20.
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.
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).
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. basal-like 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.
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.
NCT00003577.
程序性死亡配体 1（PD-L1）在实体瘤中的表达已被证明可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癌肿瘤中 PD-L1 蛋白表达的发生率和意义。
在 METABRIC 基因组研究中招募的 418 名患者的肿瘤中，评估了 CD274（PD-L1）拷贝数、转录本和蛋白水平之间的相关性。在从 SEARCH 基于人群的研究（N = 4079）和 NEAT 随机对照试验（N = 1684）中招募的 5763 名患者的组织微阵列中使用免疫组化检测 PD-L1 蛋白。
来自 SEARCH 和 NEAT 研究的 5763 个可能肿瘤中的 3916 个有 PD-L1 蛋白数据。免疫细胞表达 PD-L1 蛋白见于 6%（235/3916）的肿瘤中，肿瘤细胞表达 PD-L1 蛋白仅见于 1.7%（66/3916）的肿瘤中。PD-L1 最常表达于基底样肿瘤。这在肿瘤通过联合拷贝数和表达谱进行亚型分类时观察到[39%（17/44）的 IntClust 10 即基底样肿瘤为 PD-L1 免疫细胞阳性；P < 0.001]和使用替代 IHC 基于分类器时观察到[19%（56/302）的基底样肿瘤为 PD-L1 免疫细胞阳性；P < 0.001]。此外，五个肿瘤中观察到 CD274（PD-L1）扩增，其中四个为 IntClust 10。肿瘤细胞或浸润免疫细胞表达 PD-L1 与细胞毒性和调节性 T 细胞浸润呈正相关（P < 0.001）。在 ER 阴性疾病中，PD-L1 与改善的疾病特异性生存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）。
PD-L1 在乳腺癌中表达罕见，在基底样肿瘤中明显富集，并与浸润淋巴细胞相关。PD-L1 抑制可能有益于 19%的表达蛋白的基底样肿瘤患者。
NCT00003577。
