Available online 9 July 2022, 104577

FGFR1 and PD-L1 co-expressed in human lung cancer samples from public database.

FGFR1 activated PD-L1 via YAP in human squamous cell carcinoma.

Knockdown of FGFR1 partially reversed tumor immune evasion both in vitro and in vivo.

The combination of FGFR1 knockdown and PD-1 blockade synergistically exerted antitumor effects.

Variations in FGFR1 are common driver mutations of LSQCC. And immune checkpoint inhibitors targeting PD-1 and PD-L1 are powerful anticancer weapons. Activation of FGFR1 leads to tumorigenesis through multiple downstream molecules, including YAP, but whether and how FGFR1 regulates tumor immune evasion remain largely unclear.

LSQCC cells were modified to increase or decrease the expression of FGFR1, YAP and PD-L1, as assessed by molecular assays. After FGFR1 knockdown, cancer cells were assessed after cocultured with Jurkat T cells in vitro, and the tumor microenvironment were analyzed in C57BL/6 mice. The effect of the combination of FGFR1 knockdown and PD-1 blockade was also explored.

In human LSQCC, activation of FGFR1 was positively correlated with transcription of PD-L1. In H520 and HCC95 cells, FGFR1 upregulated PD-L1 expression via YAP, and YAP initiated the transcription of PD-L1 after binding to its promoter region. FGFR1 knockdown decreased tumor growth and reduced immune escape and reactivation of CD8+ T cells. The combination of FGFR1 knockdown and PD-1 blockade synergistically exerted antitumor effects.

The FGFR1/YAP/PD-L1 regulatory axis mediates tumor-associated immune suppression in lung squamous cell carcinoma, and FGFR1 knockdown reactivates T cells in the tumor microenvironment. Synergistic inhibition of both FGFR1 and PD-1/PD-L1 pathways may be a possible treatment for lung cancer patients.

FGFR1

PD-L1

driver mutation

tumor immune evasion

combination therapy

fibroblast growth factor receptor 1

lung squamous cell carcinoma

programmed death ligand-1

Yes-associated protein

fibroblast growth factor 2

The Cancer Genome Atlas

tumor microenvironment

transcriptional enhanced associate domain

short interfering RNAs

lymphocyte activation gene-3

tumor necrosis factor-alpha

© 2022 Published by Elsevier Inc.