FGL1 como un punto de control inmunitario en el microambiente inmunitario del cáncer de vejiga

Current treatment protocols for bladder cancer (BC) do not include additional immune checkpoint targets or biomarkers that can accurately predict treatment response. Hence, it is imperative to identify more inclusive and promising candidate compounds for immune checkpoint therapy. Therefore, we sought to investigate whether Fibrinogen Like 1 (FGL1) could serve as a new immune checkpoint for bladder cancer. Cell lines overexpressing/silencing FGL1 in human BC cells (5637, HT1376) were constructed, and the regulatory effects of FGL1 on BC cells proliferation, apoptosis, and the tumor immune microenvironment were detected using experimental techniques such as western blot, immunohistochemistry, immunofluorescence, and flow cytometry in an in vivo/vitro experimental model. Silencing FGL1 inhibited BC cells proliferation, promoted BC cells apoptosis, and stimulated tumor-infiltrating lymphocytes (TILs) activation and expansion in tumor microenvironment (TME) for antitumor immunity. Meanwhile, silencing FGL1 down-regulated the expression level of Lymphocyte Activating 3 (LAG3) to inhibit tumorigenicity in xenograft tumor models. 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.