纤维细胞
癌症研究
CD86
生物
封锁
免疫检查点
免疫疗法
SMAD公司
免疫学
免疫系统
医学
细胞生物学
转化生长因子
病理
T细胞
受体
生物化学
作者
Atsushi Mitsuhashi,Kazuya Koyama,Hirokazu Ogino,Tania Afroj,Na Thi Nguyen,Hiroto Yoneda,Kenji Otsuka,Masamichi Sugimoto,Osamu Kondoh,Hiroshi Nokihara,Masaki Hashimoto,Hiromitsu Takizawa,Tsutomu Shinohara,Yasuhiko Nishioka
出处
期刊:Cell Reports
[Elsevier]
日期:2023-03-01
卷期号:42 (3): 112162-112162
被引量:9
标识
DOI:10.1016/j.celrep.2023.112162
摘要
Recent clinical trials revealed that immune checkpoint inhibitors and antiangiogenic reagent combination therapy improved the prognosis of various cancers. We investigated the roles of fibrocytes, collagen-producing monocyte-derived cells, in combination immunotherapy. Anti-VEGF (vascular endothelial growth factor) antibody increases tumor-infiltrating fibrocytes and enhances the antitumor effects of anti-PD-L1 (programmed death ligand 1) antibody in vivo. Single-cell RNA sequencing of tumor-infiltrating CD45+ cells identifies a distinct "fibrocyte cluster" from "macrophage clusters" in vivo and in lung adenocarcinoma patients. A sub-clustering analysis reveals a fibrocyte sub-cluster that highly expresses co-stimulatory molecules. CD8+ T cell-costimulatory activity of tumor-infiltrating CD45+CD34+ fibrocytes is enhanced by anti-PD-L1 antibody. Peritumoral implantation of fibrocytes enhances the antitumor effect of PD-L1 blockade in vivo; CD86-/- fibrocytes do not. Tumor-infiltrating fibrocytes acquire myofibroblast-like phenotypes through transforming growth factor β (TGF-β)/small mothers against decapentaplegic (SMAD) signaling. Thus, TGF-βR/SMAD inhibitor enhances the antitumor effects of dual VEGF and PD-L1 blockade by regulating fibrocyte differentiation. Fibrocytes are highlighted as regulators of the response to programmed death 1 (PD-1)/PD-L1 blockade.
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