Related Experiment Video

Updated: May 26, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Osteopontin-driven TGF-β1 signaling via integrin αvβ3-NF-κB axis impairs NK cell function in head and neck squamous

Zhe Shen1,2, Xin Li1,2,3,4, Shi Luo5

  • 1Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.

Apoptosis : an International Journal on Programmed Cell Death
|May 24, 2026
PubMed

Insights

Osteopontin (OPN) in head and neck squamous cell carcinoma (HNSCC) impairs natural killer (NK) cell function by increasing TGF-β1. Targeting the OPN-TGF-β1 pathway may restore anti-tumor immunity in HNSCC patients.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) features an immunosuppressive tumor microenvironment (TME) causing natural killer (NK) cell dysfunction.
  • The precise molecular mechanisms behind NK cell impairment in HNSCC remain largely unknown.

Purpose of the Study:

  • To investigate the molecular mechanisms of NK cell dysfunction in the HNSCC TME.
  • To identify the role of osteopontin (OPN) in modulating NK cell activity within HNSCC tumors.

Main Methods:

  • Flow cytometry and multiplex immunohistochemistry for NK cell infiltration and function.
  • Bulk and single-cell RNA-sequencing (RNA-seq) for transcriptional analysis.
  • In vitro studies using tumor cell lines to assess OPN-integrin signaling pathways.

Main Results:

  • NK cells in HNSCC tumors showed reduced infiltration and activation, correlated with high OPN levels.
  • Tumor SPP1 (encoding OPN) expression inversely correlated with NK cell abundance.
  • Tumor-derived OPN activated NF-κB signaling via integrin αvβ3, leading to TGF-β1 secretion that suppressed NK cell function.

Conclusions:

  • Tumor-derived OPN drives immune evasion in HNSCC by suppressing NK cell activity through the TGF-β1 pathway.
  • The OPN-TGF-β1 axis represents a promising therapeutic target for enhancing NK cell-mediated immunity in HNSCC.
Keywords:
Head and neck squamous cell carcinomaNK cellsOsteopontinTGF-β1Tumor microenvironment

More Related Videos

A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro10:36

A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro

Published on: January 9, 2018

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...