Related Experiment Video
Updated: Feb 24, 2026
10:36
A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
Published on: January 9, 2018
7.6K
Refined Modulation of Natural Killer Cells by Transforming Growth Factor-β Isoforms
Kaku Goto1,2, Ryo Amano1, Yoshikazu Nakamura1,3
1Project Division of RNA Medical Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|February 23, 2026
Summary
Transforming growth factor-beta 3 (TGF-β3) uniquely upregulates INAVA in natural killer (NK) cells, enhancing their cancer-fighting ability. This discovery offers new avenues for cancer immunotherapy by selectively targeting TGF-β isoforms.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Natural killer (NK) cells are crucial for anti-tumor immunity.
- The tumor microenvironment, particularly transforming growth factor-beta (TGF-β), suppresses NK cell activity.
- Distinct functions of TGF-β isoforms (TGF-β1, TGF-β2, TGF-β3) are increasingly recognized.
Purpose of the Study:
- To elucidate the specific effects of TGF-β isoforms on NK cells.
- To identify novel regulators of NK cell function modulated by TGF-β isoforms.
- To explore the therapeutic potential of selective TGF-β isoform modulation.
Main Methods:
- Genome-wide gene expression analysis to identify TGF-β isoform-specific targets.
- Investigated the effect of TGF-β3 on innate immunity activator (INAVA) expression.
- Assessed the impact of INAVA on interferon gamma (IFN-γ) signaling and NK cell cytotoxicity.
- Evaluated an anti-TGF-β1 aptamer's effect on INAVA upregulation.
- Analyzed clinical data correlating INAVA expression with tumor-infiltrating NK (TINK) cells and patient survival in melanoma.
Main Results:
- TGF-β3 uniquely upregulates INAVA in NK cells, distinct from TGF-β1 and TGF-β2.
- INAVA enhances IFN-γ signaling, boosting NK cell IFN-γ release and cytotoxicity against cancer cells.
- An anti-TGF-β1 aptamer preserved TGF-β3-mediated INAVA upregulation.
- Increased INAVA expression correlated with activated TINK cells and improved survival in melanoma patients.
Conclusions:
- TGF-β3 exerts a unique immunomodulatory function on NK cells via INAVA.
- Selective modulation of TGF-β isoforms, particularly TGF-β3, represents a promising immunotherapeutic strategy.
- Targeting the TGF-β3-INAVA pathway may enhance NK cell-based cancer therapies.
Keywords:
INAVANK cellTGF‐βaptamerimmunotherapyinnate immunity activatorisoformtumor microenvironmentMore Related Videos
06:55Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
19.6K
09:54Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
3.9K
Related Concept Videos
01:16TGF - β Signaling Pathway
10.7K
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...
10.7K
02:26NF-κB-dependent Signaling Pathway
10.1K
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...
NF-κB-dependent Signaling Mechanism
The...
10.1K
01:28Cells of the Innate Immune Response
9.8K
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...
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...
9.8K
01:15Receptor Downregulation in MVBs
2.9K
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...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.9K
01:27Cytotoxic T Cells-mediated Immune Response
7.6K
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...
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...
7.6K