Related Experiment Video

Updated: Aug 13, 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

IFN-dependent down-regulation of the NKG2D ligand H60 on tumors

Jack D Bui1, Leonidas N Carayannopoulos, Lewis L Lanier

  • 1Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63310, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|January 6, 2006
PubMed

Insights

Interferons (IFNs) like IFN-gamma and IFN-alpha down-regulate H60 NKG2D ligand on mouse sarcomas. This impacts natural killer (NK) cell activity and tumor immune evasion.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Natural killer (NK) cell activity is crucial for tumor surveillance.
  • NKG2D is a key activating receptor on NK cells, recognizing its ligands on target cells.
  • Tumor cells can evade NK cell-mediated killing by modulating NKG2D ligand expression.

Purpose of the Study:

  • To investigate the effect of interferons (IFNs) on the expression of NKG2D ligands on 3'-methylcholanthrene (MCA) sarcomas.
  • To determine the functional consequences of altered NKG2D ligand expression on anti-tumor immunity.

Main Methods:

  • Flow cytometry was used to quantify H60 expression on MCA sarcomas.
  • Quantitative real-time PCR was employed to assess transcript levels.
  • Experiments involved treatment with IFN-gamma and IFN-alpha, and assessment of NK cell cytotoxicity.
  • In vivo studies utilized tumor cell transplantation and analysis of reisolated tumors.

Main Results:

  • IFN-gamma and IFN-alpha significantly reduced H60 expression on MCA sarcomas at both protein and transcript levels.
  • H60 down-regulation was dose- and time-dependent, reversible, and STAT1-dependent.
  • IFN-gamma-induced H60 reduction rendered tumors resistant to IL-2-activated NK cell killing.
  • Tumor cells reisolated from immunocompetent mice showed reduced H60 and increased MHC class I expression.

Conclusions:

  • This study demonstrates that IFNs regulate NKG2D ligand expression on murine tumors.
  • Down-regulation of H60 by IFNs contributes to tumor immune evasion by impairing NK cell recognition and killing.
  • These findings highlight a novel mechanism by which cytokines influence anti-tumor immune responses.

More Related Videos

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia05:24

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia

Published on: February 21, 2021

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells06:55

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells

Published on: February 22, 2020

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...