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三阴性与管腔 A 型乳腺癌替代亚型非转移性腋窝淋巴结免疫反应的差异。

Differences in the Immune Response of the Nonmetastatic Axillary Lymph Nodes between Triple-Negative and Luminal A Breast Cancer Surrogate Subtypes.

机构信息

Oncological Pathology and Bioinformatics Research Group, Department of Pathology, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, Tortosa, Spain; Universitat Rovira i Virgili (URV) - Campus Terres de l'Ebre, Tortosa, Spain.

Oncological Pathology and Bioinformatics Research Group, Department of Pathology, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, Tortosa, Spain.

出版信息

Am J Pathol. 2021 Mar;191(3):545-554. doi: 10.1016/j.ajpath.2020.11.008. Epub 2020 Dec 10.

Abstract

Breast cancer (BC) comprises four immunohistochemical surrogate subtypes of which triple-negative breast cancer (TNBC) has the highest risk of mortality. Axillary lymph nodes (ALNs) are the regions where BC cells first establish before distant metastasis, and the presence of tumor cells in the ALN causes an immune tolerance profile that contrasts with that of the nonmetastatic ALN (ALN). However, few studies have compared the immune components of the ALNs in BC subtypes. The present study aimed to determine whether differences between immune populations in the primary tumor and ALNs were associated with the luminal A or TNBC subtype. We evaluated a retrospective cohort of 144 patients using paraffin-embedded biopsies. The TNBC samples tended to have a higher histologic grade and proliferation index and had higher levels of immune markers compared with luminal A in primary tumors and ALNs. Two methods for validating the multivariate analysis found that histologic grade, intratumoral S100 dendritic cells, and CD8 T lymphocytes and CD57 natural killer cells in the ALNs were factors associated with TNBC, whereas CD83 dendritic cells in the ALNs were associated with the luminal A subtype. In conclusion, we found that intratumoral regions and ALNs of TNBC contained higher concentrations of markers related to immune tolerance than luminal A. This finding partially explains the worse prognosis of patients with TNBC.

摘要

乳腺癌(BC)包括四种免疫组织化学替代亚型,其中三阴性乳腺癌(TNBC)的死亡率最高。腋窝淋巴结(ALN)是 BC 细胞首先建立的区域,然后才发生远处转移,ALN 中存在肿瘤细胞会导致免疫耐受谱与非转移性 ALN(ALN)的免疫耐受谱不同。然而,很少有研究比较过 BC 亚型中 ALN 的免疫成分。本研究旨在确定原发性肿瘤和 ALN 中免疫细胞群体之间的差异是否与 luminal A 或 TNBC 亚型有关。我们使用石蜡包埋活检评估了 144 例患者的回顾性队列。与 luminal A 相比,TNBC 样本在原发性肿瘤和 ALN 中具有更高的组织学分级和增殖指数,并且具有更高水平的免疫标志物。两种验证多变量分析的方法发现,ALN 中的组织学分级、肿瘤内 S100 树突状细胞和 CD8 T 淋巴细胞以及 CD57 自然杀伤细胞是与 TNBC 相关的因素,而 ALN 中的 CD83 树突状细胞与 luminal A 亚型相关。总之,我们发现 TNBC 的肿瘤内区域和 ALN 中含有更高浓度与免疫耐受相关的标志物,这部分解释了 TNBC 患者预后较差的原因。

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