Related Experiment Video

Updated: Apr 3, 2026

Author Spotlight: A Model to Study the Systemic and Local Dynamics of CD8+ T Cells During LN Metastasis
07:45

Author Spotlight: A Model to Study the Systemic and Local Dynamics of CD8+ T Cells During LN Metastasis

Published on: January 26, 2024

3.0K

Toll-like receptor 3 regulates NK cell responses to cytokines and controls experimental metastasis

Camille Guillerey1, Melvyn T Chow2, Kim Miles2

  • 1Immunology of Cancer and Infection Laboratory; QIMR Berghofer Medical Research Institute ; Herston, Queensland, Australia ; School of Medicine; University of Queensland ; Herston, Queensland, Australia.

Oncoimmunology
|September 26, 2015
PubMed

Insights

Endogenous Toll-like receptor 3 (TLR3) signaling is crucial for natural killer (NK) cell function and immune defense against cancer metastasis. TLR3 deficiency impairs NK cell responses, highlighting its role in innate tumor immunosurveillance.

Area of Science:

  • Immunology
  • Cancer Research
  • Innate Immunity

Background:

  • Toll-like receptor 3 (TLR3) agonists like poly(I:C) enhance antitumor responses via dendritic cell (DC) and natural killer (NK) cell activation.
  • The role of endogenous TLR3 signaling in tumor immunosurveillance is largely unknown.

Purpose of the Study:

  • To investigate the role of endogenous TLR3 in modulating immune responses and controlling tumor growth without exogenous agonists.
  • To determine if TLR3 deficiency impacts spontaneous carcinogenesis and primary tumor growth.
  • To elucidate the mechanism by which TLR3 influences NK cell function and anti-metastatic immunity.

Main Methods:

  • Utilized TLR3-deficient (Tlr3 null) mice and wild-type littermates.
  • Assessed spontaneous carcinogenesis and primary tumor growth of B16F10, E0771, and MC38 cell lines.
  • Investigated experimental B16F10 lung metastasis, focusing on IFNγ secretion and NK cell activity.
  • Analyzed NK cell responsiveness to cytokine stimulation (IL-12, IL-18, IL-15) in vitro.
  • Employed bone-marrow chimera experiments to identify TLR3-expressing cell populations critical for NK cell function.
  • Examined the role of CD8α DCs and gut microbiota in TLR3-mediated immune responses.

Main Results:

  • TLR3 deficiency had minimal impact on spontaneous carcinogenesis and primary tumor growth.
  • TLR3 deficiency significantly limited experimental B16F10 lung metastasis, dependent on IFNγ and NK cells.
  • NK cells from Tlr3 null mice exhibited hyporesponsiveness to cytokine stimulation, producing reduced IFNγ.
  • Bone-marrow chimera studies indicated that TLR3 sensing on radio-sensitive immune cells is essential for competent NK cell responses.
  • CD8α DCs were not required for NK cell IFNγ production, and the defective NK cell phenotype was independent of gut microbiota.

Conclusions:

  • Endogenous TLR3 stimulation is pivotal for optimal NK cell function and anti-metastatic immunity.
  • TLR3 signaling in radio-sensitive immune cells, not CD8α DCs, is critical for NK cell activation.
  • This study reveals a novel role for endogenous TLR3 in innate tumor immunosurveillance, particularly against metastasis.
Keywords:
NK cellTLRcytokinemetastasismouse

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

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

Published on: July 20, 2019

6.6K
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

4.9K

Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
8.3K
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
10.5K
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...
3.0K
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...
10.3K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.3K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
17.4K