腫瘍DDR1は,免疫排除を誘発するためにコラーゲン繊維の配列を促進します
Xiujie Sun1, Bogang Wu1, Huai-Chin Chiang1
1Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Nature
|November 4, 2021
まとめ
ディスコイドン領域受容体1 (DDR1) は,コラーゲン繊維を並べて,トリプルネガティブ乳がんの免疫排除を誘導する. DDR1を阻害すると T細胞の浸透が促進され,腫瘍の成長が止まり,新しい免疫療法標的となる.
科学分野:
- 腫瘍学
- 免疫学
- 生物化学
背景:
- 免疫排除は,トリプルネガティブ乳がん (TNBC) の悪い結果と関連しています.
- 細胞外マトリックス (ECM) は免疫排除に寄与しますが,それを修正する現在の戦略はしばしば無効です.
- ディスコイドン領域受容体1 (DDR1) は,がんの進行に関与するコラーゲン受容体である.
研究 の 目的:
- TNBC内の免疫排除におけるDDR1の役割を調査する.
- DDR1が腫瘍の微小環境と免疫細胞の浸透に影響を与えるメカニズムを特定する.
- DDR1を抗腫瘍免疫強化の潜在的治療標的として評価する.
主な方法:
- 腫瘍の成長と免疫細胞の浸透に対するDdr1除去の効果を研究するためにTNBCのマウスモデルを使用した.
- DDR1発現とT細胞の多量性を相関させるため,ヒトTNBCサンプルを分析した.
- 遺伝子操作と抗体ベースの阻害を用いてDDR1細胞外ドメイン (DDR1-ECD) の機能を調査した.
主要な成果:
- 腫瘍におけるDdr1の消去はT細胞の浸透を増加させ,マウスモデルにおける腫瘍の成長を抑制した.
- DDR1発現はヒトTNBCにおける腫瘍内抗腫瘍T細胞と負の相関関係にある.
- DDR1-ECDはキナーゼドメインではなく,免疫排除に不可欠であり,コラーゲン繊維の配列を介し,免疫細胞の浸透を阻害しました.
結論:
- DDR1はコラーゲン繊維を並べ,T細胞の浸透を阻害することによって,TBCの免疫排除を促進します.
- DDR1をターゲットにすると,特に細胞外ドメインは,腫瘍ECMを再構成し,抗腫瘍免疫を強化し,腫瘍の成長を抑制します.
- DDR1は,TNBCおよび潜在的に他の悪性腫瘍における免疫排除を克服するための有望な免疫治療標的を表しています.
関連する概念動画
02:17The Tumor Microenvironment
7.0K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.0K
01:27Tumor Immunotherapy
731
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.
731
02:23Abnormal Proliferation
4.7K
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...
4.7K
02:07Tumor Progression
6.6K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.6K