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首页 » 癌症研究 » J Clin Cancer Res:研究人员识别早期乳腺癌免疫治疗新靶标

J Clin Cancer Res:研究人员识别早期乳腺癌免疫治疗新靶标

来源:生物谷 2014-07-23 11:39

2014年7月23讯 /生物谷BIOON/--近日,耶鲁大学癌症中心研究人员利用一种新的分子分析工具RNAScope,准确地检测出针对早期乳腺癌的免疫治疗的一个重要靶标的水平。

诊断测试使用RNAScope,测量福尔马林固定的癌组织中PD-L1(细胞程序性死亡配体PD L1)mRNA的量。(编者注:RNAscope是一种新型 RNA原位杂交技术,基于其独特的探针设计与背景抑制技术,并且融合传统RNA原位杂交技术与FISH技术的优点,使单个RNA的转录变得可视化,是目前最精准的RNA检测技术。)

PD-L1是目前几种新型免疫刺激疗法的靶标。这项研究结果发表在Clinical Cancer Research杂志上。

PD-L1是在抑制免疫应答中起重要作用的蛋白,并且在癌症中,它可以允许肿瘤逃避免疫攻击。该研究证明,约60%的早期乳腺癌有PD-L1表达,这些癌症患者体内也有大量的肿瘤浸润淋巴细胞。

高水平肿瘤浸润性淋巴细胞和PD-L1预示患者能更好地存活,这暗示两者对免疫系统具有有益的作用。Lajos Pusztai医学博士表示:这是令人兴奋的,因为这些发现为测试针对PD-L1的免疫疗法治疗乳腺癌提供了理论基础,将有助于进一步提高早期乳腺癌治愈率。

研究人员表示:高数量肿瘤浸润性淋巴细胞(tumor infiltrating lymphocytes,TIL )和高PD-L1表达的乳腺癌病人可能是针对PD-L1的免疫疗法的理想候选患者。(生物谷Bioon.com)

英文原文: Researchers identify targets for immunotherapy in early-stage breast cancer

In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas

Kurt A. Schalper,et al.

Purpose: Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas, and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemical methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas.

Experimental Design: The fluorescent RNAscope paired-primer assay was used to quantify in situ PD-L1 mRNA levels in 636 stage I–III breast carcinomas on two sets of tissue microarrays [YTMA128 (n = 238) and YTMA201 (n = 398)]. Tumor-infiltrating lymphocytes (TIL) were assessed by hematoxylin/eosin stain and quantitative fluorescence.

Results: On YTMA128 and YTMA201, 55.7% and 59.5% of cases showed PD-L1 mRNA expression, respectively. Higher PD-L1 mRNA expression was significantly associated with increased TILs (P = 0.04) but not with other clinical variables. Elevated TILs (scores 2 and 3+) occurred in 16.5% on YTMA128 and 14.8% on YTMA201 and was associated with estrogen receptor–negative status (P = 0.01 on YTMA128 and 0.0001 on YTMA201). PD-L1 mRNA expression was associated with longer recurrence-free survival (log-rank P = 0.01), which remained significant in multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the extent of TILs (HR, 0.268; CI, 0.099–0.721; P = 0.009).

Conclusions: PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased TILs and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1–targeted therapies in breast cancer.

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