将 CD84 作为打破三阴性乳腺癌免疫耐受的治疗靶点。

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-10-27 DOI:10.1016/j.celrep.2024.114920

Stav Rabani, Emine Gulsen Gunes, Martin Gunes, Bianca Pellegrino, Bar Lampert, Keren David, Raju Pillai, Aimin Li, Shirly Becker-Herman, Steven T Rosen, Idit Shachar

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引用次数: 0

摘要

三阴性乳腺癌（TNBC）是侵袭性最强的乳腺癌亚型。肿瘤微环境（TME）在 TNBC 的发展过程中起着重要的调节作用，并且受到抑制性免疫细胞的高度浸润，从而降低了抗肿瘤免疫活性。尽管调节性 B 细胞（Bregs）是 TME 的关键组成部分，但人们对它们在 TNBC 中的功能了解有限。CD84 是一种促进血液肿瘤存活的嗜同性粘附分子。在目前的研究中，我们跟踪了 CD84 在 TNBC 中调控 TME 的作用。我们证明了 CD84 在 Bregs 中诱导了一个涉及 β-catenin 和 Tcf4 通路的级联，该通路通过与白细胞介素-10 的启动子及其调节因子 AhR 的启动子结合，诱导白细胞介素-10 的转录。这将导致 Bregs 的扩增，进而控制其他免疫细胞的活性和免疫抑制。因此，我们建议将 CD84 作为打破 TNBC 免疫耐受的治疗靶点。

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CD84 as a therapeutic target for breaking immune tolerance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The tumor microenvironment (TME) plays a major regulatory role in TNBC progression and is highly infiltrated by suppressive immune cells that reduce anti-tumor immune activity. Although regulatory B cells (Bregs) are a key TME component, knowledge of their function in TNBC is limited. CD84 is a homophilic adhesion molecule that promotes the survival of blood tumors. In the current study, we followed the role of CD84 in the regulation of the TME in TNBC. We demonstrate that CD84 induces a cascade in Bregs that involves the β-catenin and Tcf4 pathway, which induces the transcription of interleukin-10 by binding to its promoter and the promoter of its regulator, AhR. This leads to the expansion of Bregs, which in turn control the activity of other immune cells and immune suppression. Accordingly, we suggest CD84 as a therapeutic target for breaking immune tolerance in TNBC.

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.