Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome
Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome
复制标题
DOI：
10.1111/his.12904
复制
发表时间：
2016-07-01
期刊：
影响因子：
6.4
通讯作者：
O'Toole, Sandra A.
中科院分区：
文献类型：
--
作者：
Beckers, Rhiannon K.;Selinger, Christina I.;O'Toole, Sandra A.
aimstri3阴性乳腺癌（TNBC）患者通常预后较差；迫切需要确定更有效的治疗策略。针对黑色素瘤和非小细胞肺癌的程序性死亡1/程序性死亡配体1 （PD1/PDL1）的临床试验报道了高反应率，肿瘤PDL1表达被认为是一种潜在的生物标志物，可以丰富患者对这些治疗的反应。迄今为止，只有非常有限的数据报道了TNBC中PDL1的表达。方法和结果对161例原发性tnbc进行spdl1免疫组化，评估肿瘤及间质室免疫细胞的变化。PDL1在TNBC中表达非常普遍，表达于肿瘤细胞膜（64%）、细胞质（80%）和间质（93%）细胞间室。细胞质肿瘤表达PDL1与较低的乳腺癌特异性死亡风险相关[危险比（HR） 0.45, P = 0.035]，而间质PDL1表达与较低的全因死亡率相关（HR 0.305, P = 0.0042）。膜性PDL1表达与预后无关。虽然PDL1表达和肿瘤浸润淋巴细胞都与更好的预后相关，但只有淋巴血管浸润和高肿瘤浸润淋巴细胞是乳腺癌特异性死亡的独立预后因素。结论虽然PDL1在TNBC中表达频繁，但它并不是独立的预后因素。结果的差异取决于PDL1表达的细胞区室。考虑到肿瘤浸润淋巴细胞（til）和PDL1表达在该队列中的临床意义，这些数据为研究免疫检查点疗法在TNBC中的效用提供了进一步的动力。
AimsTriple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC.Methods and resultsPDL1 immunohistochemistry was performed on 161 primary TNBCs and assessed in the tumour as well as immune cells in the stromal compartment. PDL1 expression was very common in TNBC, expressed in the tumour cell membrane (64%), cytoplasm (80%) and stromal (93%) cellular compartments. Cytoplasmic tumoral expression of PDL1 was associated with a lower risk of breast cancer-specific death [hazard ratio (HR) 0.45, P = 0.035] while stromal PDL1 expression was associated with a lower rate of deaths from all causes (HR 0.305, P = 0.0042). Membranous expression of PDL1 was not associated with outcome. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only lymphovascular invasion and high tumour-infiltrating lymphocytes were independently prognostic for breast cancer-specific death.ConclusionWhile PDL1 expression is frequent in TNBC, it was not independently prognostic. There were differences in outcome depending on the cellular compartment of PDL1 expression. These data provide further impetus for investigating the utility of immune checkpoint therapies in TNBC, given the clinical significance of tumour-infiltrating lymphocytes (TILs) and PDL1 expression in this cohort.