γδ T 細胞は,αβ T 細胞の活性化を抑制することによって,臓腫瘍形成をサポートする
Donnele Daley1, Constantinos Pantelis Zambirinis1, Lena Seifert1
1S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
Cell
|August 30, 2016
まとめ
臓がんでは ガンマ・デルタ・T細胞という 特定のタイプのT細胞が 抗腫瘍免疫を抑制します これらの細胞を遮断すると 他のT細胞を活性化させ 臓管内腺癌の新たな治療戦略を提案します
科学分野:
- 免疫学
- 腫瘍学
- 癌 研究
背景:
- 炎症は 臓がんの発生に 重要な役割を果たします
- ガンマデルタT細胞 (γδT細胞) は,臓管内腺がん (PDA) の腫瘍微環境の重要な構成要素である.
研究 の 目的:
- 臓がんの進行における γδT 細胞の役割を調査する.
- γδT細胞が抗腫瘍免疫に影響を与えるメカニズムを探求する.
- PDAにおける γδT細胞を標的とした治療戦略を評価する.
主な方法:
- ヒトPDAにおける γδT細胞群の識別と特徴付け
- γδT細胞募集に関与するケモカイン信号の分析.
- γδT細胞の実験的な枯渇または阻害
- γδT細胞調節後のαβT細胞応答の評価
- γδT細胞の免疫チェックポイントリガンド発現 (例えば,PD-L1) の評価
- γδT細胞を標的とする腫瘍の保護を評価するインビボ試験.
主要な成果:
- γδT細胞は,ヒトPDAにおける腫瘍浸透性T細胞の約40%を占める.
- γδT細胞の募集は,様々なケモカイン信号によって調節される.
- γδT細胞の除去または阻害は,PDAに対する保護効果を示した.
- γδT細胞の切除により,αβT細胞の浸透,活性化,Th1偏化が強化された.
- PDAに浸透する γδT細胞は,適応性抗腫瘍免疫を抑制する枯渇リガンドを発現する.
- γδT細胞に対するPD- L1の阻害は,CD4 ((+)) とCD8 ((+)) T細胞の浸透と免疫性を増加させ,腫瘍に対する保護をもたらした.
結論:
- γδT細胞は,臓がんにおけるエフェクターT細胞の活性化の中心的調節体である.
- γδT細胞は,PDAにおける免疫抑制チェックポイントリガンドの重要な源として作用する.
- γδT細胞,特にそのチェックポイントリガンド発現を標的とした治療は,臓がんに対する有望な治療法である.
さらに関連する動画
関連する概念動画
Cancer-Critical Genes II: Tumor Suppressor Genes
10.0K
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...
10.0K
Cancer-Critical Genes I: Proto-oncogenes
11.8K
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...
11.8K
Tumor Immunotherapy
2.1K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.1K
mTOR Signaling and Cancer Progression
5.0K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.0K
Abnormal Proliferation
5.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
TGF - β Signaling Pathway
10.8K
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...
10.8K


