Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation.

Autor: Chaudhuri SM; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Weinberg SE; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Wang D; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Yalom LK; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Montauti E; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Iyer R; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Tang AY; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Torres Acosta MA; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Medical Scientist Training Program, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Shen J; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Mani NL; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Wang S; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Liu K; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Lu W; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Bui TM; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Manzanares LD; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Dehghani Z; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Wai CM; Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Gao B; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Wei J; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Yue F; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Cui W; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Singer BD; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Sumagin R; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Zhang Y; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Fang D; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: fangd@northwestern.edu.
Jazyk: angličtina
Zdroj: Cell reports. Medicine [Cell Rep Med] 2024 Mar 19; Vol. 5 (3), pp. 101441. Date of Electronic Publication: 2024 Feb 29.
DOI: 10.1016/j.xcrm.2024.101441
Abstrakt: While immunotherapy has revolutionized cancer treatment, its safety has been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory (T reg ) cell function specifically in the tumor microenvironment. T reg cell-specific MED1 deletion does not predispose mice to autoimmunity or excessive inflammation. In contrast, MED1 is required for T reg cell promotion of tumor growth because MED1 is required for the terminal differentiation of effector T reg cells in the tumor. Suppression of these terminally differentiated T reg cells is sufficient for eliciting antitumor immunity. Both human and murine T reg cells experience divergent paths of differentiation in tumors and matched tissues with non-malignant inflammation. Collectively, we identify a pathway promoting the differentiation of a T reg cell effector subset specific to tumors and demonstrate that suppression of a subset of T reg cells is sufficient for promoting antitumor immunity in the absence of autoimmune consequences.
Competing Interests: Declaration of interests B.D.S. holds United States Patent No. US 10,905,706 B2, “Compositions and Methods to Accelerate Resolution of Acute Lung Inflammation” and serves on the Scientific Advisory Board of Zoe Biosciences, outside of the submitted work.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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