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激素受体的表达与乳腺癌微环境的特定免疫特征相关

英文原题:Expression of hormone receptors is associated with specific immunological profiles of the breast cancer microenvironment.

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Expression of hormone receptors is associated with specific immunological profiles of the breast cancer microenvironment.

PubMed 2023/01/31(内容时间) Breast Cancer Res Q1 · IF 6.2(JCR 2025)

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研究概要

激素受体表达与乳腺癌微环境中特定免疫学特征在基因和蛋白表达水平上相关。

研究思路结论见上方概要

阐明乳腺癌微环境中独特的免疫调节机制可能有助于开发新的治疗策略。一些研究表明,激素受体也具有免疫调节功能,但其机制尚未完全明了。在本研究中,我们全面分析了雌激素受体(ER)、孕激素受体(PgR)和雄激素受体(AR)的表达与乳腺癌免疫特征之间的关系。

利用公开可用的基因表达谱数据集METABRIC和SCAN-B,分析了激素受体表达与通过CIBERSORTx算法估算的乳腺癌组织中免疫细胞组成之间的关联。我们对45例乳腺癌组织样本进行了组织学评估,包括TIL(肿瘤浸润淋巴细胞)(hTIL)、PD-L1(hPD-L1)表达,以及通过流式细胞术(FCM)检测11种免疫细胞的浸润情况。分析了这些指标与通过免疫组化评估的肿瘤组织中ER、PgR和AR表达之间的关系。

ESR1、PGR和AR的表达与总体免疫组成呈负相关。ER和AR的表达,而非PgR的表达,与hTIL和hPD-L1表达呈负相关。FCM分析显示,ER和AR的表达,而非PgR的表达,与总白细胞浸润减少相关。CIBERSORTx和FCM分析均显示,ER表达与巨噬细胞和CD4+ T细胞浸润减少相关,AR表达与巨噬细胞浸润减少相关。

展开英文摘要原文

Elucidating the unique immunoregulatory mechanisms in breast cancer microenvironment may help develop new therapeutic strategies. Some studies have suggested that hormone receptors also have immune regulatory functions, but their mechanisms are not fully understood. In this study, we have comprehensively analyzed the relationship between the expressions of estrogen (ER), progesterone (PgR), and androgen receptors (AR), and the immunological profile in breast cancer.

Using publicly available gene expression profile datasets, METABRIC and SCAN-B, the associations between the expressions of hormone receptors and the immune cell compositions in breast cancer tissue, estimated by CIBERSORTx algorithm, were analyzed. We histologically evaluated tumor-infiltrating lymphocytes (hTIL), PD-L1 (hPD-L1) expression, and the infiltration of 11 types of immune cells by flow cytometry (FCM) for 45 breast cancer tissue samples. The relationships between them and the expressions of ER, PgR, and AR of tumor tissues, evaluated immunohistochemically, were analyzed.

Expressions of ESR1, PGR, and AR were negatively correlated with overall immune composition. Expressions of ER and AR, but not that of PgR, were inversely associated with hTIL and hPD-L1 expression. FCM analysis showed that the expressions of ER and AR, but not that of PgR, were associated with decreased total leukocyte infiltration. Both CIBERSORTx and FCM analysis showed that ER expression was associated with reduced infiltration of macrophages and CD4+ T cells and that of AR with reduced macrophage infiltration.

Hormone receptor expression correlates with specific immunological profiles in the breast cancer microenvironment both at the gene and protein expression levels.

论文信息

作者
Hanamura T、Kitano S、Kagamu H、Yamashita M、Terao M、Okamura T、Kumaki N、Hozumi K
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
Breast cancer research : BCR2023 Jan 31
原文标识
PubMed 36721218 · DOI 10.1186/s13058-023-01606-7