Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression.
Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression.
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DOI：
10.1186/s12967-018-1458-y
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发表时间：
2018-04-04
影响因子：
7.4
通讯作者：
Ohira M
中科院分区：
文献类型：
--
作者：
Asano Y;Kashiwagi S;Goto W;Takada K;Takahashi K;Morisaki T;Fujita H;Takashima T;Tomita S;Ohsawa M;Hirakawa K;Ohira M
“避免免疫破坏”最近被确定为癌症的标志之一。程序性细胞死亡（PD）-1/程序性细胞死亡配体（PD-L）1途径是一种重要的免疫抑制机制，可以让癌细胞逃避宿主免疫。本研究调查了这些免疫检查点蛋白的表达如何影响乳腺癌新辅助化疗（NAC）的反应。共有 177 名可切除的早期乳腺癌患者接受了 NAC 治疗。通过免疫组织化学评估雌激素受体、孕激素受体、人表皮生长因子受体 2、Ki67、PD-L1、PDL-2 和 PD-1 状态。其中37例（20.9%）患者PD-1高表达，42例（23.7%）患者PD-L1高表达，52例（29.4%）患者PD-L2高表达。 PD-1和PD-L1高表达的患者三阴性乳腺癌（TNBC）的发生率显着较高（p = 0.041）（p < 0.001）。在 TNBC 中，PD-1 和 PD-L1 高表达的患者非 pCR 率显着较高 (p = 0.003) (p < 0.001)。单变量分析显示，PD-1和PD-L1表达也显着缩短TNBC的无病生存期（p = 0.048，HR = 3.318）（p = 0.007，HR = 8.375）。然而，多变量分析发现，只有PD-L1表达是独立的预后因素（p = 0.041，HR = 9.479）。 PD-1 和 PD-L1 表达可能可用作预测乳腺癌 NAC 治疗反应的生物标志物。最重要的是，PD-L1 表达也可能可用作 TNBC 更有效化疗的生物标志物。本文的在线版本 (10.1186/s12967-018-1458-y) 包含补充材料，可供授权用户使用。
“Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry. There were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p < 0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p < 0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479). PD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC. The online version of this article (10.1186/s12967-018-1458-y) contains supplementary material, which is available to authorized users.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.5
作者：
Konishi, J;Yamazaki, K;Nishimura, M
通讯作者：
Nishimura, M
影响因子：
8.4
作者：
Houssami, Nehmat;Macaskill, Petra;Mamounas, Eleftherios
通讯作者：
Mamounas, Eleftherios
DOI：
10.1073/pnas.192461099
发表时间：
2002-09-17
影响因子：
11.1
作者：
Iwai, Y;Ishida, M;Minato, N
通讯作者：
Minato, N