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CD47 抗原在 Reed-Sternberg 细胞中的表达作为经典型霍奇金淋巴瘤的一个新的潜在生物标志物。

Expression of CD47 antigen in Reed-Sternberg cells as a new potential biomarker for classical Hodgkin lymphoma.

机构信息

Department of Hematology, Alvarez Buylla Hospital, Mieres, Asturias, Spain.

Department of Pathology, University Hospital Central de Asturias, Oviedo, Asturias, Spain.

出版信息

Clin Transl Oncol. 2020 May;22(5):782-785. doi: 10.1007/s12094-019-02171-2. Epub 2019 Jul 29.

Abstract

INTRODUCTION

CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha on macrophages inhibiting phagocytic signal, providing a survival advantage to tumor. CD47, therefore, represents a valuable target for immunotherapy and is currently under clinical investigation. We aimed to study CD47 expression in Hodgkin Reed Sternberg cells (HRS).

METHODS

We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine patients had advanced disease. Bulk disease was present in one patient. Normal lymphoid tissue and normal prostate epithelium were used as normal controls as recommended by manufacturer. Approval from the Local Ethical committee was obtained before any analysis.

RESULTS

CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells.

DISCUSSION

We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.

摘要

简介

CD47 的过表达已在几种肿瘤亚型中报道。CD47 与巨噬细胞上的 SIRPalpha 相互作用,抑制吞噬信号,为肿瘤提供生存优势。因此,CD47 代表了免疫治疗的一个有价值的靶点,目前正在临床研究中。我们旨在研究霍奇金氏 Reed-Sternberg 细胞(HRS)中 CD47 的表达。

方法

我们在我们机构从 2016 年 10 月至 2018 年 1 月期间获得的 16 例新诊断的、未经选择的患者(8 名女性,8 名男性)的经典霍奇金淋巴瘤(CHL)肿瘤组织芯片上,测试了一种多克隆 CD47 抗体(LifeSpan Biosciences,西雅图,WA)表达,以及经典的 HRS 细胞标志物。组织学亚型包括 11 例结节性硬化,3 例混合细胞性,2 例富含淋巴细胞。中位年龄为 53 岁(范围:8 至 74 岁)。根据 EORTC 和 GHSG 标准,3 例患者为早期疾病且无不良预后因素,1 例患者有不良预后因素,9 例患者为晚期疾病。1 例患者存在肿块性疾病。按照制造商的建议,正常淋巴组织和正常前列腺上皮组织用作正常对照。在进行任何分析之前,均获得了当地伦理委员会的批准。

结果

CD47 在 13/13 例 CHL 中均在所有 HRS 细胞上过度表达,具有特征性的点状模式。HRS 细胞明显比浸润性 T 细胞和基质细胞更强烈地表达 CD47。

讨论

我们提出,HRS 细胞通过上调 CD47,可能避免肿瘤生长中的固有免疫检查,这可以通过使用阻断单克隆抗体来规避。

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