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Updated: May 13, 2026

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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

GBP2 enhances anti-PD-L1 response in colorectal cancer via GSDMD-mediated YAP nuclear translocation by non-pyroptotic

Haihang Nie1,2,3,4, Yali Yu1,2,3, Jingkai Zhou1,2,3

  • 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Oncogene
|May 11, 2026
PubMed

Insights

Guanylate-binding protein 2 (GBP2) enhances immune checkpoint blockade (ICB) therapy in colorectal cancer (CRC) by regulating the gasdermin D (GSDMD)-Yes-associated protein (YAP) pathway, overcoming immune resistance.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Immune checkpoint blockade (ICB) therapy shows limited efficacy in most colorectal cancers (CRC) due to inherent immune resistance.
  • Understanding the mechanisms of immune evasion in CRC is crucial for developing effective treatments.

Purpose of the Study:

  • To identify key regulators of ICB response in colorectal cancer.
  • To elucidate the role of guanylate-binding protein 2 (GBP2) in modulating anti-tumor immunity and ICB efficacy.

Main Methods:

  • Analysis of CRC patient cohorts, patient-derived organoids, and preclinical mouse models.
  • Investigation of the interaction between GBP2, gasdermin D (GSDMD), and Yes-associated protein (YAP) signaling.
  • Assessment of tumor immune infiltration and response to anti-PD-L1 therapy following genetic or pharmacologic manipulation.

Main Results:

  • GBP2 was identified as a critical enhancer of ICB response by modulating the GSDMD-YAP axis.
  • GBP2 directly binds GSDMD, inhibiting its activation and preventing YAP nuclear translocation, which is crucial for T-cell recruitment.
  • Inhibition of GSDMD restored YAP inactivation and sensitized tumors to anti-PD-L1 therapy, demonstrating therapeutic potential.

Conclusions:

  • A novel GBP2-GSDMD-YAP signaling axis was defined, which plays a significant role in immune evasion in colorectal cancer.
  • Targeting this axis, particularly through GSDMD inhibition, represents a promising strategy to overcome ICB resistance in CRC.

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