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成人 T 细胞白血病/淋巴瘤中 CD47 和 SIRPα 的免疫组织化学表达的临床病理分析。

Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma.

机构信息

Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan.

出版信息

Hematol Oncol. 2020 Dec;38(5):680-688. doi: 10.1002/hon.2768. Epub 2020 Aug 8.

Abstract

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces "don't eat me signal", leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.

摘要

CD47 和信号调节蛋白 alpha(SIRPα)的相互作用诱导“不要吃我信号”,导致吞噬作用受到抑制。该信号可能影响恶性疾病的临床过程。尽管 CD47 和 SIRPα 的表达与几种肿瘤的临床病理特征相关,但成人 T 细胞白血病/淋巴瘤(ATLL)的研究尚未得到充分记录。本研究旨在阐明 CD47 和 SIRPα 表达与 ATLL 临床病理特征之间的关系。我们对 73 个活检样本进行了免疫组化染色,发现 CD47 主要在肿瘤细胞中表达,而 SIRPα 在非肿瘤性基质细胞中表达。CD47 阳性病例的 FoxP3 表达明显更高(P =.0232),CCR4 表达明显更低(P =.0214)。SIRPα 阳性病例的总生存期明显长于 SIRPα 阴性病例(P =.0132)。SIRPα 阳性病例的 HLA Ⅰ类(P =.0062)、HLA Ⅱ类(P =.0133)、微环境 PD-L1(miPD-L1)(P =.0032)和 FoxP3(P =.0229)阳性表达明显更高。单因素分析显示,SIRPα 表达与预后显著相关(风险比 [HR] 0.470;95%置信区间 [CI] 0.253-0.870;P =.0167),尽管多因素分析并未显示 SIPRα 为独立预后因素。基质细胞中 SIRPα 的表达反映了肿瘤微环境中激活的免疫监视机制,并诱导 ATLL 预后良好。对基因表达或基因组异常的更详细研究将揭示 CD47 和 SIRPα 在 ATLL 中的临床和生物学意义。

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