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首页> 外文期刊>EBioMedicine >FOXP1 negatively regulates tumor infiltrating lymphocyte migration in human breast cancer
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FOXP1 negatively regulates tumor infiltrating lymphocyte migration in human breast cancer

机译：FOXP1负调节人类乳腺癌中肿瘤浸润的淋巴细胞迁移

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Background FOXP1, a transcriptional regulator of lymphocyte development, is abnormally expressed in some human tumors. This study investigated FOXP1-mediated regulation of tumor infiltrating lymphocytes (TIL) in untreated primary breast cancer (BC). Methods FOXP1 expression was analyzed in tissues from primary untreated breast tumors, BC cell lines and the METABRIC gene expression BC dataset. Cytokine and chemokine expression and lymphocyte migration in response to primary tumor supernatants (SN) was compared between FOXP1suphi/sup and FOXP1suplo/sup primary BC. Finding FOXP1 expression was higher in estrogen receptor positive compared to negative BC. FOXP1suphi/sup tumors were significantly associated with lower TIL and fewer tertiary lymphoid structures (TLS) compared to FOXP1suplo/sup BC. Silencing FOXP1 in BC cell lines positively impacted cytokine and chemokine expression with the inverse effect associated with overexpression. CXCL9 , CXCL10 , CXCL11 , CXCL13 , CX3CL , CCL20 , IL2 , IL21 , GZMB and IFNG expression decreased while IL10 and TGFβ increased in FOXP1suphi/sup compared to FOXP1suplo/sup primary BC. Lymphocyte migration using primary BC supernatants detected decreased mobility toward FOXP1suphi/sup supernatants. FOXP1suplo/sup BC expresses higher levels of chemokines driving TIL migration. The METABRIC gene expression dataset analysis show FOXP1 expression is associated with unfavorable BC outcomes. Interpretation These data identify FOXP1 as an important negative regulator of immune responses in BC via its regulation of cytokine and chemokine expression. Fund Belgian Fund for Scientific Research (FNRS 3.4513.12F) and Opération Télévie (7.4636.13F and 7.4609.15F), Fonds J.C. Heuson and Fonds Lambeau-Marteaux.
机译：背景FOXP1是淋巴细胞发育的转录调节因子，在某些人类肿瘤中异常表达。这项研究调查了FOXP1介导的未经治疗的原发性乳腺癌（BC）中肿瘤浸润淋巴细胞（TIL）的调节。方法分析FOXP1在未经治疗的原发性乳腺肿瘤，BC细胞系和METABRIC基因表达BC数据集中的组织中的表达。比较了FOXP1 hi 和FOXP1 lo 原发性BC的细胞因子和趋化因子表达以及淋巴细胞迁移对原发肿瘤上清液（SN）的响应。发现FOXP1表达在雌激素受体阳性中比在阴性BC中更高。与FOXP1 lo BC相比，FOXP1 hi 肿瘤与较低的TIL和更少的三级淋巴样结构（TLS）显着相关。在BC细胞系中沉默FOXP1会积极影响细胞因子和趋化因子的表达，而与过度表达相关的逆作用。与FOXP1 hi 相比，FOXP1 hi 中的CXCL9，CXCL10，CXCL11，CXCL13，CX3CL，CCL20，IL2，IL21，GZMB和IFNG表达降低，而IL10和TGFβ升高。使用原代BC上清液的淋巴细胞迁移检测到对FOXP1 hi 上清液的迁移率降低。 FOXP1 lo BC表达更高水平的趋化因子驱动TIL迁移。 METABRIC基因表达数据集分析表明，FOXP1表达与不利的BC结果有关。解释这些数据表明，FOXP1通过调节细胞因子和趋化因子的表达，是BC中免疫反应的重要负调节剂。比利时科学研究基金（FNRS 3.4513.12F）和特利维歌剧院（7.4636.13F和7.4609.15F），Fonds J.C. Heuson和Fonds Lambeau-Marteaux。

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