Platelet factor 4-induced T H 1-T reg polarization suppresses antitumor immunity.

Autor: Kuratani A; Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan., Okamoto M; Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan., Kishida K; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.; Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan., Okuzaki D; Genome Information Research Center, Osaka University, Suita, Osaka, Japan., Sasai M; Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.; Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka, Japan.; Center for Advances Modalities and Drug Delivery Systems, Osaka University, Suita, Osaka, Japan., Sakaguchi S; Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan., Arase H; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.; Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.; Center for Advances Modalities and Drug Delivery Systems, Osaka University, Suita, Osaka, Japan.; Department of Immunochemistry, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka, Japan., Yamamoto M; Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.; Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka, Japan.; Center for Advances Modalities and Drug Delivery Systems, Osaka University, Suita, Osaka, Japan.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Nov 22; Vol. 386 (6724), pp. eadn8608. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1126/science.adn8608
Abstrakt: The tumor microenvironment (TME) contains a number of immune-suppressive cells such as T helper 1-polarized regulatory T cells (T H 1-T reg cells). However, little is known about the mechanism behind the abundant presence of T H 1-T reg cells in the TME. We demonstrate that selective depletion of arginase I (Arg1)-expressing tumor-associated macrophages (Arg1 + TAMs) inhibits tumor growth and concurrently reduces the ratio of T H 1-T reg cells in the TME. Arg1 + TAMs secrete the chemokine platelet factor 4 (PF4), which reinforces interferon-γ (IFN-γ)-induced T reg cell polarization into T H 1-T reg cells in a manner dependent on CXCR3 and the IFN-γ receptor. Both genetic PF4 inactivation and PF4 neutralization hinder T H 1-T reg cell accumulation in the TME and reduce tumor growth. Collectively, our study highlights the importance of Arg1 + TAM-produced PF4 for high T H 1-T reg cell levels in the TME to suppress antitumor immunity.
Databáze: MEDLINE
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