Panoply™ Human FGFR1 Knockdown Stable Cell Line

FGFR1 gene mutations are common driver mutations in squamous cell carcinoma (LSQCC). Immune checkpoint inhibitors targeting PD-1 and PD-L1 are potent anti-cancer weapons. FGFR1 activation promotes tumorigenesis through multiple downstream molecules, including YAP, but whether and how FGFR1 regulates tumor immune escape remains unclear. Here, the study shows that in human LSQCC, FGFR1 activation is positively correlated with PD-L1 transcription. In H520 and HCC95 cells, FGFR1 upregulates PD-L1 expression via YAP, which binds to the PD-L1 promoter region and initiates PD-L1 transcription. FGFR1 knockdown inhibits tumor growth, reduces immune escape, and induces CD8+ T cell reactivation. Combined use of FGFR1 knockdown and PD-1 blockade produces a synergistic anti-tumor effect. These results suggest that synergistic inhibition of the FGFR1 and PD-1/PD-L1 pathways may be a potential therapeutic approach for lung cancer patients.

To simulate the interaction between cancer cells and immune cells, researchers established a co-culture system. Suspended Jurkat T cells were added to adherent FGFR1 knockdown or control cancer cells, which were treated with human PD-1 antibody (nivolumab) or control antibody (isotype IgG). After 72 hours of co-culture, the suspended cells were removed, and cancer cell proliferation was assessed. Crystal violet staining showed that FGFR1 knockdown reduced cell viability, and FGFR1 knockdown combined with nivolumab treatment significantly reduced cell viability (Figure 1A). Cell counting experiments confirmed this result (Figure 1B). After co-culture, Jurkat T cells were removed, and their immune escape markers and immunostimulatory cytokines were stained. In the experimental group (co-cultured with FGFR1 knockdown cancer cells), the expression of PD-1 (Figure 1C) and lymphocyte activation gene-3 (LAG-3) (Figure 1D) was significantly reduced, while the expression of interleukin-2 (IL-2) (Figure 1E) was increased. There was no significant difference in the expression of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) (Figure 1F, G). These results indicate that FGFR1 inhibition partially reverses tumor immune escape in vitro.

Figure 1. FGFR1 knockdown partially reversed immune evasion in vitro. (Lu M, et al., 2022)