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以 TIL(肿瘤浸润淋巴细胞)和 PD-L1 表达为代表的乳腺癌微环境免疫学特征

英文原题:Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression.

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Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression.

PubMed 2022/05/16(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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研究概要

这些结果表明,hTILs 反映了肿瘤微环境中免疫应答的差异,并且某些免疫细胞组分在乳腺癌微环境的 PD-L1 通路中有利表达。

中文摘要

TIL(肿瘤浸润淋巴细胞)(TILs)和程序性细胞死亡1配体1(PD-L1)是某些乳腺癌亚型已确立的预后和预测生物标志物。然而,它们与免疫反应复杂性之间的关联尚未完全明了。因此,我们分析了乳腺癌组织中免疫细胞组分与组织学评估的TIL(hTIL)和PD-L1(hPD-L1)之间的关联。从乳腺癌患者中收集了45份肿瘤样本和18份血液样本。通过流式细胞术评估了总白细胞计数、11种免疫细胞群体的频率以及各细胞组分中PD-L1的表达。分别通过苏木精-伊红染色和免疫组织化学评估TILs和PD-L1。较高的hTIL评分与白细胞浸润增加、CD4+和CD8+T细胞比例升高以及NK 细胞和自然杀伤T细胞比例降低相关。PD-L1在肿瘤中的非经典单核细胞、单核细胞/巨噬细胞、髓源性抑制细胞、髓系树突状细胞、树突状细胞及其他谱系中高表达。hPD-L1阳性准确反映了这些组分中PD-L1的表达,以及肿瘤中白细胞浸润的增加。这些结果表明,hTILs反映了肿瘤微环境中免疫反应的差异,并且某些免疫细胞组分在乳腺癌微环境的PD-L1通路中有利表达。

展开英文摘要原文

Tumor-infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1) are established prognostic and predictive biomarkers for certain breast cancer subsets. However, their association with the immune response complexity is not fully understood. Therefore, we analyzed the association between the immune cell fractions in breast cancer tissues and histologically assessed TIL (hTIL) and PD-L1 (hPD-L1). Forty-five tumor and eighteen blood samples were collected from patients with breast cancer. Total leukocyte counts, frequency of 11 immune cell populations, and PD-L1 expression in each cell fraction were evaluated by flow cytometry. TILs and PD-L1 were assessed by hematoxylin and eosin staining and immunohistochemistry, respectively. A higher hTIL score showed association with increased leukocyte infiltration, higher CD4 + and CD8 + T cell proportions, and lower natural killer and natural killer T cell proportions. PD-L1 was highly expressed in nonclassical monocytes, monocyte/macrophages, myeloid-derived suppressor cells, myeloid dendritic cells, dendritic cells, and other lineages in tumors. hPD-L1 positivity reflected PD-L1 expression accurately in these fractions, as well as increased leukocyte infiltration in tumors. These results indicate that hTILs reflect differences in the immune responses in the tumor microenvironment, and certain immune cell fractions are favorably expressed in the PD-L1 pathway in breast cancer microenvironments.

论文信息

作者
Hanamura T、Kitano S、Kagamu H、Yamashita M、Terao M、Tsuda B、Okamura T、Kumaki N
第一作者单位
Department of Breast Oncology, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa Prefecture, 259-1193, Japan.Japan
通讯作者单位
Department of Breast Oncology, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa Prefecture, 259-1193, Japan. niikura@is.icc.u-tokai.ac.jp.Japan
文献类型
非美国政府资助研究
期刊
Scientific reports2022 May 16
原文标识
PubMed 35577913 · DOI 10.1038/s41598-022-11578-x