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Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future.人类癌症的抗PD-1/PD-L1疗法:过去、现在与未来。
J Clin Invest. 2015 Sep;125(9):3384-91. doi: 10.1172/JCI80011. Epub 2015 Sep 1.
2
PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes.乳腺癌中 PD-L1 蛋白表达罕见,在基底样肿瘤中富集,并与浸润淋巴细胞相关。
Ann Oncol. 2015 Jul;26(7):1488-93. doi: 10.1093/annonc/mdv192. Epub 2015 Apr 20.
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PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer.PD-L1 表达与乳腺癌肿瘤浸润淋巴细胞及新辅助化疗反应的相关性。
Cancer Immunol Res. 2015 Apr;3(4):326-32. doi: 10.1158/2326-6066.CIR-14-0133. Epub 2014 Dec 19.
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Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.癌症患者对抗PD-L1抗体MPDL3280A反应的预测性相关因素。
Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011.
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PD-L1 expression in triple-negative breast cancer.PD-L1 在三阴性乳腺癌中的表达。
Cancer Immunol Res. 2014 Apr;2(4):361-70. doi: 10.1158/2326-6066.CIR-13-0127. Epub 2014 Jan 10.
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In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas.原位肿瘤 PD-L1 mRNA 表达与乳腺癌中浸润 T 细胞增加和更好的预后相关。
Clin Cancer Res. 2014 May 15;20(10):2773-82. doi: 10.1158/1078-0432.CCR-13-2702. Epub 2014 Mar 19.
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Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial.肿瘤浸润淋巴细胞在三阴性乳腺癌中具有预后价值,并可预测早期乳腺癌曲妥珠单抗获益:FinHER 试验结果。
Ann Oncol. 2014 Aug;25(8):1544-50. doi: 10.1093/annonc/mdu112. Epub 2014 Mar 7.
8
Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer.肿瘤浸润 CD8+ 淋巴细胞是乳腺癌原发系统性治疗病理完全缓解的独立预测因素。
Br J Cancer. 2013 Nov 12;109(10):2705-13. doi: 10.1038/bjc.2013.634. Epub 2013 Oct 15.
9
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.抗 PD-L1 抗体在晚期癌症患者中的安全性和活性。
N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
10
Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer.肿瘤浸润淋巴细胞是乳腺癌患者新辅助化疗的重要病理预测指标。
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PD-L1 的表达减弱了高水平肿瘤浸润淋巴细胞对三阴性乳腺癌预后的积极影响。

Expression of PD-L1 Attenuates the Positive Impacts of High-level Tumor-infiltrating Lymphocytes on Prognosis of Triple-negative Breast Cancer.

机构信息

a Department of Breast Surgery , Shengjing Hospital of China Medical University , Shenyang , Liaoning Province , China.

b Department of Pathology , Penn State College of Medicine , Hershey , PA , USA.

出版信息

Cancer Biol Ther. 2019;20(8):1105-1112. doi: 10.1080/15384047.2019.1595282. Epub 2019 Mar 31.

DOI:10.1080/15384047.2019.1595282
PMID:30929569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6605986/
Abstract

: Among all breast cancer subtypes, triple-negative breast cancer (TNBC) has aggressive clinical manifestations including more frequent relapses and metastases. The roles of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in TNBC clinicopathological behaviors and patients' survival outcomes remain unclear. : TNBC (108 cases) patients with at least 5-year follow-up were analyzed for PD-L1 expression and TILs by immunohistochemistry. We also analyzed the relationships between PD-L1 expression, TILs and clinicopathological characteristics. Furthermore, we explored the effect of PD-L1 expression and TILs on prognosis as illustrated by disease-free survival (DFS). : The expression of PD-L1 was related to more aggressive clinicopathological behaviors in TNBC patients including a larger tumor size, higher incidence of PL-1-ALN, more frequent distant metastasis, and a reduced disease-free survival. In contrast, patients with high-level TILs showed less aggressive disease progression hence a better prognosis compared to patients with low-level TILs. Among patients with high-level TILs, PD-L1 expression was correlated with adverse prognosis. : Expression of PD-L1 and low-level TILs in TNBC patients were associated with adverse clinical outcomes. However, the positive impact of high-level TILs was attenuated by PD-L1 expression. Our results suggest potential biomarkers for a selection of indicated cases in the TNBC patients for anti-PD-L1/anti-PD1 immunotherapy.

摘要

三阴性乳腺癌(TNBC)的临床表现较为激进,包括更频繁的复发和转移,在所有乳腺癌亚型中,TNBC 较为特殊。PD-L1 表达和肿瘤浸润淋巴细胞(TILs)在 TNBC 临床病理行为和患者生存结局中的作用尚不清楚。

我们通过免疫组化分析了至少有 5 年随访的 108 例 TNBC 患者的 PD-L1 表达和 TILs。我们还分析了 PD-L1 表达、TILs 与临床病理特征之间的关系。此外,我们通过无病生存(DFS)来探讨 PD-L1 表达和 TILs 对预后的影响。

PD-L1 的表达与 TNBC 患者更具侵袭性的临床病理行为相关,包括肿瘤体积较大、PL-1-ALN 发生率较高、远处转移更频繁,以及无病生存率降低。相比之下,高水平 TILs 的患者疾病进展较为缓慢,预后较好,而低水平 TILs 的患者则相反。在高水平 TILs 的患者中,PD-L1 表达与不良预后相关。

TNBC 患者的 PD-L1 表达和低水平 TILs 与不良临床结局相关。然而,高水平 TILs 的积极影响被 PD-L1 表达所减弱。我们的结果表明,这些标志物可能有助于选择 TNBC 患者进行抗 PD-L1/抗 PD1 免疫治疗。