FGL1 (Fibrinogen Like 1)

Our data demonstrated that refining immunotherapy delivery approaches can improve tolerability that ultimately transforms treatment success.

This study provides novel insights into the therapeutic potential of FGL1 in inflammatory liver disorders by modulating macrophage function and promoting liver repair. These results highlight its potential as a novel anti-inflammatory therapeutic agent for the treatment of inflammatory liver diseases.

Specifically, we elucidate the molecular mechanisms underlying their involvement in hepatitis progression, metabolic-associated fatty liver disease pathogenesis, and hepatocellular carcinoma tumorigenesis. Furthermore, we highlight their therapeutic potential in hepatic disease management, particularly emphasizing that targeting the FGL1/lymphocyte activation gene 3 immune checkpoint axis represents a novel paradigm in precision cancer immunotherapy.

Targeting the FGL1/LAG3 signaling pathway can stimulate bladder cancer TILs activation and expansion for antitumor immunity in TME, which inhibits tumor proliferation and growth and promotes tumor apoptosis. Therefore, FGL1 can be used as a potential immune checkpoint for the treatment of BC.

KEGG analysis revealed that DEGs were involved in signal pathways such as combined proteoglycan interaction, glycoprotein hormone and peptide hormone biosynthesis, non-integrin membrane-extracellular matrix interaction, and protein digestion and absorption, and the top 20 key genes of GC were identified, including OASL, ISG20, RAB3A, CREM, BIRC7, LHB, etc. FGL1 is a potential biomarker for the diagnosis and prognosis of GC. FGL1-mediated signaling pathways may be a new target for GC therapy in future.

FGL1 plays a pivotal role in CDDP resistance development by activating the Integrinβ1-dependent pro-survival pathway in laryngeal carcinoma. Therapeutic targeting of FGL1 may represent a promising strategy to circumvent chemoresistance and improve clinical outcomes for CDDP-resistant laryngeal cancer patients.

We elucidated the role of FGL1 in NSCLC, proposing that FGL1 acts like a "shield machine cutter" in mediating T1 NSCLC N2 lymph node tube formation, creating metastasis channels. This provides the basis for novel FGL1-targeting treatment strategies.

Additionally, the generation of abundant reactive oxygen species (ROS) under ultrasound irradiation induces immunogenic cell death (ICD), thereby promoting dendritic cell maturation and cytotoxic T cell infiltration to amplify anti-PD-1 efficacy. Our findings demonstrate that NTNDs can effectively restore the ability of T cells to eliminate anti-PD-1-resistant tumors, suggesting a promising strategy for overcoming immunoresistance in cancer treatment.

We observed that FGL1 expression was repressed during MASLD progression in mice and humans concomitantly with the severity of liver injury. Altogether, these findings suggest that FGL1 is not a major contributor to the pathogenesis of MASLD and HCC.

Furthermore, treatment with a STAT3 inhibitor significantly inhibited the IL-6-induced FGL1 expression and EMT in NSCLC cells. IL-6 regulates FGL1 expression to mediate metastasis and EMT of NSCLC cells through the STAT3 signaling pathway.

Specifically, unchanged or elevated CD155 expression after NACT was associated with poor disease-specific survival. Further more, high CD155 expression after chemotherapy was related to decreased CD8+ T cell infiltration and poor outcome in TNBC.