Research advances in FGL1/LAG3 for cancer diagnosis and treatment: From basics to clinical practice

Fibrinogen-like protein 1 (FGL1), a liver-secreted protein involved in proliferation and metabolism, and lymphocyte activation gene 3 (LAG3), an immune checkpoint receptor expressed on the surfaces of various activated immune cells, play critical roles in tumor immunology. Numerous studies have confirmed that FGL1 acts as a ligand for LAG3 and mediates immune evasion by tumor cells. This review aims to provide a comprehensive summary of the research progress in FGL1/LAG3 in terms of its expression, role in the tumor microenvironment, and clinical application. The expression and regulation of FGL1/LAG3 are influenced by multiple cytokines and signaling pathways. In the tumor microenvironment, FGL1/LAG3 modulates tumor cell proliferation, invasion, and migration through mechanisms such as epithelial-mesenchymal transition, gene methylation, oxygen metabolism, and lipid metabolism. FGL1/LAG3 can serve as a prognostic biomarker, independently or in combination with PD-L1/PD-1, and can be targeted using monoclonal antibodies, bi-specific antibodies, and dual-targeted vaccines to restore the proliferation and activation potential of T cells. Additionally, FGL1/LAG3 has demonstrated therapeutic potential when combined with targeted therapies, radiotherapy, traditional Chinese medicine, and adoptive cell therapy. Overall, FGL1/LAG3 plays a pivotal role in cancer initiation, progression, diagnosis, treatment, and prognosis.