CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Expression of PD-L1 in Early-Stage Invasive Breast Carcinoma and Its Relation to Tumor-Infiltrating Lymphocytes.
Expression of PD-L1 in Early-Stage Invasive Breast Carcinoma and Its Relation to Tumor-Infiltrating Lymphocytes.
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尽管 PD-L1 对早期 BC 预后的影响尚未明确,但我们的结果表明,PD-L1 在早期阶段是一个负向预后标志物。PD-L1 可作为高级别早期乳腺癌患者的新治疗靶点。
免疫治疗靶点已成为乳腺癌(BC)尤其是晚期三阴性亚型(TNBC)中有前景的治疗方法之一。然而,程序性细胞死亡配体1(PD-L1)靶向治疗在其他BC亚型中,尤其是在早期癌中的作用研究较少。本研究旨在探讨PD-L1在不同分子亚型早期浸润性BC中的表达率,并阐明其与TIL(肿瘤浸润淋巴细胞)(TILS)密度(细胞毒性T细胞和调节性T细胞)、已确立的临床病理因素及患者预后之间的关系。
我们的研究纳入了109例早期BC病例。根据免疫组化数据将病例分为五种分子亚型。对所有研究病例进行PD-L1、FOXP3和CD8免疫染色分析。PD-L1表达与CD8+细胞毒性T细胞、FOXP3+调节性T细胞、组织病理学参数、BC分子亚型、7年无病生存期(DFS)和总生存期(OS)相关。
PD-L1在所研究的早期BC病例中表达率为11%。它与高肿瘤分级(p= <0.001)、转移发生(p=0.037)、高FOXP3+ T细胞密度(p= <0.001)和低CD8+ T细胞密度(p= <0.001)显著相关。PD-L1表达在TNBC中较高(16.1%),其次是HER2/neu富集组(14.3%)。所有luminal A病例均显示PD-L1表达阴性。发现PD-L1是患者生存的独立预后因素(DFS;p=0.031和OS:p=0.04)。
Immunotherapeutic targets became one of the promising approaches in breast cancer (BC), especially in advanced stage triple-negative subtype (TNBC). However, the role of programmed cell death ligand 1 (PD-L1) targeting in other BC subtypes, especially in early-stage carcinoma is less explored. We aimed in this study to investigate the prevalence of PD-L1 in early-stage invasive BC of different molecular subtypes and to elucidate its relation to tumor-infiltrating lymphocytes (TILS) density (cytotoxic and regulatory T-cells), established clinicopathological factors and patients' outcome. MATERIAL AND METHODS: One hundred and nine cases of early-stage BC were enrolled in our study. Cases were classified into five molecular subtypes according to the Immunohistochemical data. PD-L1, FOXP3 and CD8 immunostaining were analyzed for all studied cases. PD-L1 expression was correlated with CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells, histopathologic parameters, BC molecular subtypes, 7-years disease-free survival (DFS) and overall survival (OS).
PD-L1 was expressed in 11% of the studied early-stage BC cases. It showed a significant correlation with high tumor grade (p= <0.001), development of metastasis (p=0.037), high FOXP3+ T-cell density (p= <0.001) and low CD8+ T-cells density (p= <0.001). PD-L1 expression was higher in TNBC (16.1%), followed by HER2/neu-enriched group (14.3%). All luminal A cases showed negative PD-L1 expression. PD-L1 was found to be an independent prognostic factor for patients' survival (DFS; p=0.031 and OS: p=0.04).
Although the impact of PD-L1 on early-stage BC outcomes had not been clearly established, our results indicated that PD-L1 is a negative prognostic marker in early settings. PD-L1 can serve as a new therapeutic target for patients with high-grade early-stage breast carcinoma.
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