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

Autor:	Rabani S; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Gunes EG; Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA, USA., Gunes M; Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA, USA., Pellegrino B; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Lampert B; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., David K; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Pillai R; Pathology Core, Beckman Research Institute, City of Hope, Duarte, CA, USA., Li A; Pathology Core, Beckman Research Institute, City of Hope, Duarte, CA, USA., Becker-Herman S; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Rosen ST; Department of Hematology and Stem Cell Transplantation, City of Hope and Beckman Research Institute, Duarte, CA, USA., Shachar I; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: idit.shachar@weizmann.ac.il.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Oct 27; Vol. 43 (11), pp. 114920. Date of Electronic Publication: 2024 Oct 27.
DOI:	10.1016/j.celrep.2024.114920
Abstrakt:	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. Competing Interests: Declaration of interests S.T.R. and I.S. have stock options as founders in SLAMBio. This potential conflict of interest has been reviewed and managed by the Weizmann and COH Conflict of Interest in Research Committees. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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