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T 细胞浸润的组成在不同分子亚型的原发性浸润性乳腺癌以及根据肿瘤大小和淋巴结状态而有所不同。

The composition of T cell infiltrates varies in primary invasive breast cancer of different molecular subtypes as well as according to tumor size and nodal status.

机构信息

Department of Pathomorphology, Jagiellonian University Medical College, ul. Grzegórzecka 16, 31-531, Kraków, Poland.

Department of General, Oncological, and Gastrointestinal Surgery, Jagiellonian University Medical College, Kraków, Poland.

出版信息

Virchows Arch. 2019 Jul;475(1):13-23. doi: 10.1007/s00428-019-02568-y. Epub 2019 Apr 17.

Abstract

T lymphocytes are the most numerous immune cells in tumor-associated infiltrates and include several subpopulations of either anticancer or pro-tumorigenic functions. However, the associations between levels of different T cell subsets and breast cancer molecular subtypes as well as other prognostic factors have not been fully established yet. We performed immunohistochemistry for CD8 (cytotoxic T cells (CTL)), FOXP3 (regulatory T cells (Tregs)), and GATA3 (Th2 cells) in 106 formalin-fixed paraffin-embedded invasive breast cancer tissue samples and analyzed both the numbers and percentages of investigated cells in tumor-associated infiltrates. We observed that triple-negative breast cancer (TNBC) and HER2+ non-luminal breast tumors were associated with more numerous CTLs and Tregs and a higher Treg/Th2 cell ratio as compared with luminal A subtype. A higher Treg percentage was related to a decreased hormone receptor expression, an increase in the Ki67 level, a greater tumor size of luminal tumors, and the presence of lymph node metastases. Moreover, differences in the composition of T cell infiltrates were associated with HER2 status and histologic grade and type, and a distinct immune pattern was observed in tumors of different phenotypes regarding pT stage and nodal status. The results of our work show the diversity of T cell infiltrates in primary invasive breast cancers of different phenotypes and suggest that progression of luminal or non-luminal tumors is related to distinct tumor-associated T cell composition.

摘要

T 淋巴细胞是肿瘤相关浸润物中数量最多的免疫细胞,包括具有抗癌或促肿瘤功能的几个亚群。然而,不同 T 细胞亚群水平与乳腺癌分子亚型以及其他预后因素之间的关联尚未完全确定。我们对 106 例福尔马林固定石蜡包埋的浸润性乳腺癌组织样本进行了 CD8(细胞毒性 T 细胞(CTL))、FOXP3(调节性 T 细胞(Treg))和 GATA3(Th2 细胞)的免疫组织化学染色,并分析了肿瘤相关浸润物中研究细胞的数量和百分比。我们观察到,与 luminal A 亚型相比,三阴性乳腺癌(TNBC)和 HER2+非 luminal 乳腺癌肿瘤与更多的 CTL 和 Treg 以及更高的 Treg/Th2 细胞比值相关。较高的 Treg 百分比与激素受体表达降低、Ki67 水平升高、luminal 肿瘤的肿瘤大小增加以及淋巴结转移的存在有关。此外,T 细胞浸润组成的差异与 HER2 状态和组织学分级和类型相关,并且不同表型的肿瘤在 pT 分期和淋巴结状态方面观察到不同的免疫模式。我们工作的结果显示了不同表型的原发性浸润性乳腺癌中 T 细胞浸润的多样性,并表明 luminal 或非 luminal 肿瘤的进展与特定的肿瘤相关 T 细胞组成有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b30/6611750/eb77bf388004/428_2019_2568_Fig1_HTML.jpg

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