Immune checkpoint therapy has achieved significant efficacy by blocking inhibitory pathways to release the function of T lymphocytes. In the clinic, anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) have progressed to first-line monotherapies in certain tumor types. However, the efficacy of anti-PD-1/PD-L1 mAbs is still limited due to toxic side effects and de novo or adaptive resistance. Moreover, other immune checkpoint target and biomarkers for therapeutic response prediction are still lacking; as a biomarker, the PD-L1 (CD274, B7-H1) expression level is not as accurate as required. Hence, it is necessary to seek more representative predictive molecules and potential target molecules for immune checkpoint therapy. Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related protein secreted by the liver. Multiple studies have confirmed that FGL1 is a newly emerging checkpoint ligand of lymphocyte activation gene 3 (LAG3), emphasizing the potential of targeting FGL1/LAG3 as the next generation of immune checkpoint therapy. In this review, we summarize the substantial regulation mechanisms of FGL1 in physiological and pathological conditions, especially tumor epithelial to mesenchymal transition, immune escape and immune checkpoint blockade resistance, to provide insights for targeting FGL1 in cancer treatment.

中文翻译：

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纤维蛋白原样蛋白 1 (FGL1)：下一个免疫检查点目标

免疫检查点疗法通过阻断抑制性通路释放 T 淋巴细胞的功能，取得了显着的疗效。在临床上，抗程序性细胞死亡蛋白 1/程序性细胞死亡配体 1 (PD-1/PD-L1) 单克隆抗体 (mAbs) 已发展为某些肿瘤类型的一线单一疗法。然而，由于毒副作用和从头或适应性耐药，抗 PD-1/PD-L1 mAb 的功效仍然有限。此外，仍然缺乏用于治疗反应预测的其他免疫检查点靶标和生物标志物；作为生物标志物，PD-L1（CD274、B7-H1）的表达水平并不像要求的那么准确。因此，有必要为免疫检查点治疗寻找更具代表性的预测分子和潜在的靶分子。纤维蛋白原样蛋白 1 (FGL1) 是一种由肝脏分泌的增殖和代谢相关蛋白。多项研究证实，FGL1是淋巴细胞激活基因3（LAG3）的新兴检查点配体，强调了靶向FGL1/LAG3作为下一代免疫检查点疗法的潜力。在这篇综述中，我们总结了 FGL1 在生理和病理条件下的实质调控机制，特别是肿瘤上皮间质转化、免疫逃逸和免疫检查点阻断抵抗，为在癌症治疗中靶向 FGL1 提供见解。强调靶向 FGL1/LAG3 作为下一代免疫检查点疗法的潜力。在这篇综述中，我们总结了 FGL1 在生理和病理条件下的实质调控机制，特别是肿瘤上皮间质转化、免疫逃逸和免疫检查点阻断抵抗，为在癌症治疗中靶向 FGL1 提供见解。强调靶向 FGL1/LAG3 作为下一代免疫检查点疗法的潜力。在这篇综述中，我们总结了 FGL1 在生理和病理条件下的实质调控机制，特别是肿瘤上皮间质转化、免疫逃逸和免疫检查点阻断抵抗，为在癌症治疗中靶向 FGL1 提供见解。