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Last update 08 May 2025

FGL2

Last update 08 May 2025

Basic Info

Synonyms

FGL2, fibrinogen like 2, Fibrinogen-like protein 2

+ [3]

Introduction

May play a role in physiologic lymphocyte functions at mucosal sites.

Drugs associated with FGL2

HCMV-IE1mut-FGL2 172-220

Target

FGL2

Mechanism

FGL2 agonists

Active Org.

Qingdao University

Originator Org.

Qingdao University

Active Indication

Glioblastoma Multiforme

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with FGL2

100 Translational Medicine associated with FGL2

0 Patents (Medical) associated with FGL2

333

Literatures (Medical) associated with FGL2

01 May 2025·Cancer Letters

Fibrinogen-like 2 in tumor-associated macrophage-derived extracellular vesicles shapes an immunosuppressive microenvironment in colorectal liver metastases by promoting tumor stemness and neutrophil extracellular traps formation

Article

Author: Zhou, Menghua ; Zhou, Mantang ; Liu, Youdong ; Chen, Weiwei ; Guan, Bingjie ; Xie, Bowen ; Zhao, Senlin ; Gu, Qi ; Yan, Dongwang ; Xiang, Jianjun ; Zhao, Qian

Investigating the mechanisms underlying the development of an immunosuppressive microenvironment within colorectal liver metastases (CRLM) is important for identifying synergistic targets for immunotherapy. The regulatory role of tumor-associated macrophage-derived extracellular vesicles (TAM-EVs) in the immune microenvironment of CRLM has not yet been fully explored. Here, we found that TAM-EVs shaped the immunosuppressive microenvironment at the invasive front in murine CRLM models, thus dampening anti-PD-1 immunotherapy. This environment is characterized by an increased tumor stemness potential and abundant neutrophil extracellular traps (NETs) formation. Mechanistically, TAM-EVs-derived fibrinogen-like 2 (FGL2) interacts with the FCGR2B receptor in tumor cells, which further activates a p-STAT3/IL-1β positive feedback loop to increase the stemness potential of cancer cells, whereas IL-1β mediates the communication between cancer cells and neutrophils. The use of an anti-IL-1β monoclonal antibody can reduce NETs production and synergize with anti-PD-1 immunotherapy, which offers clinical translational significance for CRLM therapy. The FGL2/p-STAT3/IL-1β loop correlates with an immunosuppressive microenvironment and poor prognosis in human patients with CRLM. Our results revealed the potential of enhancing the efficacy of immunotherapy via the targeted clearance of NETs using anti-IL-1β monoclonal antibodies, which have significant clinical translational value in the treatment of CRLM.

08 Apr 2025·JCI Insight

Fgl2 regulates FcγRIIB+CD8+ T cell responses during infection

Article

Author: Langelier, Charles R ; Maier, Cheryl L ; Kraft, Colleen S ; Rouphael, Nadine ; Woodworth, Michael H ; Adelman, Max W ; Scharer, Christopher D ; Ford, Mandy L ; Morris, Anna B ; Martinez, Catherine D ; Bennion, Kelsey B ; McCook, Kem-Maria

While the inhibitory receptor FcγRIIB has been shown to be upregulated on activated CD8+ T cells in both mice and humans, its effect on T cell fate during infection has not been fully elucidated. We identified an increase in FcγRIIB-expressing CD8+ T cells in patients with COVID-19 relative to healthy controls as well as in mouse models of viral infection. Despite its well-known role as an Fc receptor, FcγRIIB also ligates the immunosuppressive cytokine Fgl2, resulting in CD8+ T cell apoptosis. Both chronic LCMV infection in mice and COVID-19 in humans resulted in a significant increase in plasma Fgl2. Transfer of CD8+ T cells into a Fgl2-replete, but not Fgl2-devoid, environment resulted in elimination of FcγRIIB+, but not FcγRIIB-, CD8+ T cells. Similarly, plasma Fgl2 was directly proportional to CD8+ T cell lymphopenia in patients with COVID-19. RNA-Seq analysis demonstrated that Fgl2 was produced by murine virus-specific CD8+ T cells, with an increase in Fgl2 in CD8+ T cells elicited during chronic versus acute viral infection. Fgl2 was also upregulated in CD8+ T cells from patients with COVID-19 versus healthy controls. In summary, CD8+ T cell production of Fgl2 during viral infection underpinned an FcγRIIB-mediated loss of CD8+ T cell immunity in both mice and humans.

01 Apr 2025·Gene

Role of fibrinogen-like 2 (FGL2) proteins in implantation: Potential implications and mechanism

Review

Author: Zhang, Yuanzhen ; Kang, Jiawei ; Wang, Yueying ; Wang, Mei

Fibrinogen-like (Fgl2) protein belongs to fibrinogen super family, which catalyzes the conversion of prothrombin to thrombin and is involved in the coagulation process. There are two different forms of functional Fgl2 protein: membrane associated Fgl2 (mFgl2) and soluble Fgl2 (sFgl2). mFgl2, as a type II transmembrane protein with property with prothrombinase activity from its N-terminal fragment, was extensively secreted or expressed by inflammatory macrophages, dendritic cells (DCs), Th1 cells and endothelial cells. While sFgl2 was mainly produced by regulatory T cells (Tregs) and then secreted into the vasculature, which contributes to autoimmune disease by regulating maturation of (DCs), polarization of macrophage, inhibiting T cell proliferation and differentiation and inducing apoptosis of B cells. In particular, emerging evidence has shown that Fgl2 is implicated in female reproductive system that contributes to embryo development, ovarian granulosa cells differentiation and implantation failure. This article summarizes the role and potential mechanisms of Fgl2 in reproduction and identifies research gaps along with the future directions.

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FGL2

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