日本大阪大学Masahiro Yamamoto团队近期取得重要工作进展，他们研究发现了血小板因子4 （PF4）诱导的T_H1-T_reg极化抑制抗肿瘤免疫。相关研究成果2024年11月22日出版的《科学》杂志发表了这项成果。

据介绍，肿瘤微环境（TME）包含许多免疫抑制细胞，如T辅助1极化调节性T细胞（T_H1 T_reg细胞）。然而，对于TME中T_H1-T_reg细胞大量存在背后的机制知之甚少。

研究人员证明，选择性耗竭表达精氨酸酶I（Arg1）的肿瘤相关巨噬细胞（Arg1⁺ TAM）可以抑制肿瘤生长，同时降低TME中T_H1-T_reg细胞的比例。Arg1⁺ TAM分泌趋化因子PF4，其以依赖于CXCR3和IFN-γ受体的方式，增强干扰素-γ（IFN-γ）诱导的T_reg细胞极化为T_H1-T_reg细胞。PF4基因失活和PF4中和都会阻碍T_H1-T_reg细胞在TME中的积聚，并减少肿瘤生长。

总之，这一研究强调了Arg1⁺ TAM产生的PF4，对TME中高T_H1-T_reg细胞水平抑制抗肿瘤免疫的重要性。

附：英文原文

Title: Platelet factor 4–induced TH1-Treg polarization suppresses antitumor immunity

Author: Ayumi Kuratani, Masaaki Okamoto, Kazuki Kishida, Daisuke Okuzaki, Miwa Sasai, Shimon Sakaguchi, Hisashi Arase, Masahiro Yamamoto

Issue&Volume: 2024-11-22

Abstract: The tumor microenvironment (TME) contains a number of immune-suppressive cells such as T helper 1–polarized regulatory T cells (TH1-Treg cells). However, little is known about the mechanism behind the abundant presence of TH1-Treg 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 TH1-Treg cells in the TME. Arg1+ TAMs secrete the chemokine platelet factor 4 (PF4), which reinforces interferon-γ (IFN-γ)–induced Treg cell polarization into TH1-Treg cells in a manner dependent on CXCR3 and the IFN-γ receptor. Both genetic PF4 inactivation and PF4 neutralization hinder TH1-Treg cell accumulation in the TME and reduce tumor growth. Collectively, our study highlights the importance of Arg1+ TAM–produced PF4 for high TH1-Treg cell levels in the TME to suppress antitumor immunity.

DOI: adn8608

Source: https://www.science.org/doi/10.1126/science.adn8608