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Updated: Jun 2, 2025

Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
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Published on: March 24, 2017

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VISTA-induced tumor suppression by a four amino acid intracellular motif

Yan Zhao1, Tina Andoh1, Fatima Charles1

  • 1Departments of Medicine and Molecular Biology, Cecil H. and Ida Green Center for Reproductive Sciences, UT Southwestern Medical Center, Dallas, TX, 75235.

Biorxiv : the Preprint Server for Biology
|January 13, 2025
PubMed

Insights

VISTA

Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Signaling

Background:

  • VISTA is an immune checkpoint receptor investigated for cancer immunotherapy.
  • Its precise signaling pathways are not fully understood.
  • Understanding VISTA's cell-intrinsic functions is crucial for developing novel cancer treatments.

Purpose of the Study:

  • To elucidate the intracellular signaling mechanisms of VISTA.
  • To identify the role of VISTA in cancer cell proliferation.
  • To explore VISTA's potential as a therapeutic target in breast cancer.

Main Methods:

  • Identification of a conserved NPGF motif in VISTA.
  • Investigating the interaction between VISTA, NUMB, and Rab11.
  • Analyzing VISTA expression and EGFR signaling in triple-negative breast cancer models.
  • Utilizing mouse models to assess the impact of VISTA NPGF domain mutations.

Main Results:

  • A conserved NPGF motif in VISTA suppresses cell proliferation by regulating growth receptor signaling.
  • VISTA's NPGF motif sequesters NUMB, disrupting epidermal growth factor receptor (EGFR) trafficking and signaling.
  • High VISTA expression correlates with low proliferation in triple-negative breast cancers.
  • Mutating the VISTA NPGF domain reverses VISTA-induced growth suppression in preclinical models.

Conclusions:

  • VISTA utilizes the NPGF motif to control malignant epithelial cell growth and signaling via NUMB sequestration.
  • This VISTA-mediated pathway suppresses tumor growth independently of immune system engagement.
  • The identified intracellular VISTA signaling mechanism offers potential therapeutic targets for cancer immunotherapy.

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