T-ヘルパー-1-細胞サイトカインは,がんを老化へと駆り立てます
Heidi Braumüller1, Thomas Wieder, Ellen Brenner
1Department of Dermatology, Eberhard Karls University, Liebermeister Strasse 25, 72076 Tübingen, Germany.
Nature
|February 5, 2013
まとめ
腫瘍免疫は,T細胞とインターフェロン-ガンマ (IFN-γ) を通じてがんの成長を止めることができる. IFN-γと腫瘍死滅因子 (TNF) の組み合わせは,癌細胞の永久的な成長停止を誘導し,老化と呼ばれるプロセスを引き起こします.
科学分野:
- 免疫学 免疫学とは
- 癌生物学 癌生物学について
- 細胞生物学 細胞生物学
背景:
- 適応免疫は,癌の制御のために死とクリアランスメカニズムを使用します.
- T細胞とインターフェロン-γ (IFN-γ) によってがんの成長を効率的に抑制するには,増殖を止めるための追加の未定義のメカニズムが必要です.
研究 の 目的:
- T-ヘルパー-1-細胞のサイトカイン,特にIFN-γおよび腫瘍死滅因子 (TNF) が,癌の永久的な成長停止を誘発する役割を調査する.
- 癌におけるサイトカイン誘発の衰老の基礎となる分子メカニズムを解明する.
主な方法:
- シミアンウイルス40大T抗原 (Tag) を発現するマウスモデルを利用して,衰弱したp53とRb経路を持つ腫瘍を作成しました.
- タグ発現がんにIFN-γとTNFを併用した.
- 評価された細胞サイクル停止 (G1/G0),p16INK4a活性化,Rb低酸化,STAT1およびTNFR1シグナル伝達.
- タグ発現がんにおけるTヘルパー1細胞とTNFR1シグナル伝達のインビボの役割を調査した.
主要な成果:
- IFN-γとTNFの組み合わせは,Tag発現がんにおける永久的なG1/G0成長停止を誘発し,p16INK4aを活性化し,Rb低酸化につながります.
- このサイトカイン誘発の衰老には,STAT1とTNFR1のシグナル伝達が必要です.
- In vivoでは,Tヘルパー1細胞はIFN-γおよびTNFR1-依存の衰老を誘導し,Tag発現がんを永久に停止します.
- TNFR1が欠けているがんは,サイトカイン誘発の衰老に抵抗し,攻撃的な成長を示します.
結論:
- IFN-γとTNFの結合作用は,がんにおける永久的な成長停止 (老化) を直接誘導する.
- このサイトカイン誘発の衰老は,がんの進行を阻止する一般的なメカニズムであり,STAT1とTNFR1のシグナル伝達を必要とします.
- これらの経路をターゲットにすることで,がん制御のための新しい戦略を提供することができます.
関連する概念動画
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
01:27Cytotoxic 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...
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...
01:24T 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...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
02:53Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:53Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...