FGFR pathway inhibition enhances PD-1 blockade and modulates antitumor immunity in colorectal cancer models.
8 affiliations
- 1Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
- 2Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.
- 3Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- 4Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- 5Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. [email protected].
- 6Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. [email protected].
- 7Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. [email protected].
- 8Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China. [email protected].
Abstract
Immune checkpoint blockade (ICB) has demonstrated limited efficacy in microsatellite stable (MSS) colorectal cancer (CRC). The fibroblast growth factor receptor (FGFR) signaling pathway contributes to tumor immune evasion, yet its role in CRC remains insufficiently understood. We investigated the immunomodulatory effects of FGFR inhibition in combination with PD-1 blockade in murine CRC models. In vitro co-culture systems were used to evaluate T cell activation upon FGFR3 blockade. RNA sequencing and bioinformatics analyses, including The Cancer Genome Atlas (TCGA) dataset evaluation, were conducted to elucidate molecular mechanisms and clinical relevance. Combined FGFR inhibition and PD-1 blockade significantly reduced T cell exhaustion and promoted macrophage repolarization toward an antitumor phenotype. Transcriptomic profiling revealed upregulation of immune-related pathways and activation of immune-stimulatory genes. In vitro, FGFR3-specific monoclonal antibody treatment enhanced IFNg release following PD-1 blockade. Moreover, analysis of TCGA data demonstrated that high FGFR3 expression correlates with worse prognosis in CRC patients. Our findings suggest that FGFR pathway inhibition may enhance the efficacy of immune checkpoint blockade and provide a rationale for further investigation of FGFR-targeted combination strategies in MSS CRC.
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BibTeX
@article{shang2026fgfr,
title = {{FGFR pathway inhibition enhances PD-1 blockade and modulates antitumor immunity in colorectal cancer models.}},
author = {Zhou Shang and Changqing Jing and Jiyuan Liu and Baolin Zhang and Marta Rúbies Bedós and Irineos Papakyriacou and Yumeng Mao and Yuezhi Chen},
journal = {BMC cancer},
year = {2026},
month = oct,
doi = {10.1186/s12885-026-17105-9},
url = {https://europepmc.org/article/MED/42875754},
note = {CC BY},
}
RIS
TY - JOUR
TI - FGFR pathway inhibition enhances PD-1 blockade and modulates antitumor immunity in colorectal cancer models.
AU - Zhou Shang
AU - Changqing Jing
AU - Jiyuan Liu
AU - Baolin Zhang
AU - Marta Rúbies Bedós
AU - Irineos Papakyriacou
AU - Yumeng Mao
AU - Yuezhi Chen
PY - 2026
DA - 2026/10/13
JO - BMC cancer
DO - 10.1186/s12885-026-17105-9
UR - https://europepmc.org/article/MED/42875754
AB - Immune checkpoint blockade (ICB) has demonstrated limited efficacy in microsatellite stable (MSS) colorectal cancer (CRC). The fibroblast growth factor receptor (FGFR) signaling pathway contributes to tumor immune evasion, yet its role in CRC remains insufficiently understood. We investigated the immunomodulatory effects of FGFR inhibition in combination with PD-1 blockade in murine CRC models. In vitro co-culture systems were used to evaluate T cell activation upon FGFR3 blockade. RNA sequencing and bioinformatics analyses, including The Cancer Genome Atlas (TCGA) dataset evaluation, were conducted to elucidate molecular mechanisms and clinical relevance. Combined FGFR inhibition and PD-1 blockade significantly reduced T cell exhaustion and promoted macrophage repolarization toward an antitumor phenotype. Transcriptomic profiling revealed upregulation of immune-related pathways and activation of immune-stimulatory genes. In vitro, FGFR3-specific monoclonal antibody treatment enhanced IFNg release following PD-1 blockade. Moreover, analysis of TCGA data demonstrated that high FGFR3 expression correlates with worse prognosis in CRC patients. Our findings suggest that FGFR pathway inhibition may enhance the efficacy of immune checkpoint blockade and provide a rationale for further investigation of FGFR-targeted combination strategies in MSS CRC.
SN - 1471-2407
ER -