酵素核の球状核酸は,腫瘍の低酸素を緩和することによって,強化されたクプロプトーシスと抗腫瘍免疫反応を可能にします
Yuting Huang1, Xueliang Liu1, Jiawei Zhu1
1Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200240, China.
Journal of the American Chemical Society
|March 29, 2024
まとめ
この研究では,腫瘍の酸素濃度を増やすことで,銅による細胞死 (クプロプトーシス) を強化するナノプラットフォームを導入した. このアプローチは抗がん免疫反応を高め 長期的な免疫を促進します
科学分野:
- 生物医学工学
- ナノテクノロジー
- 癌 免疫学
背景:
- 銅に依存する細胞死であるクプロプトーシスは免疫反応を活性化しますが,低酸素腫瘍の微小環境によって妨げられます.
- 低酸素症は抗腫瘍免疫とクプロプトーシス感受性を抑制し,治療効果を制限する.
研究 の 目的:
- 銅イオンを放出する ナノプラットフォームを開発して カプロプトーシスを誘発し 腫瘍低酸素症を克服する
- 免疫抑制性腫瘍の微小環境を緩和し,抗腫瘍免疫力を高める.
主な方法:
- CAT-ecSNA-Cuナノプラットフォームを作成するために,ロールリングサークル増幅 (RCA) によるCpG配列を含むDNAで機能化されたカタラーゼ (CAT).
- H2O2をO2に変換し,ミトコンドリアの呼吸を促進し,クプロプトーシスを敏感にします.
- 低酸素誘導因子-1 (HIF-1) と免疫細胞の活性化に対する酸素濃度の増加の影響を調査した.
主要な成果:
- CAT-ecSNA-Cuナノプラットフォームは 銅イオンを成功裏に放出し 胞を敏感にし 腫瘍の酸素化を増加させました
- HIF-1の発現を抑制し,免疫抑制性腫瘍の微小環境を減少させた.
- クプロプトーシスは免疫細胞死 (ICD) を誘発し,TLR9の活性化によってデンドリット細胞 (DC) の成熟と抗原の表示を促進します.
- チェックポイント阻害剤 (αPD- L1) と併用したクプロプトーシスは,PD- L1を上調することによって抗腫瘍免疫を強めた.
結論:
- 開発されたナノプラットフォームは,低酸素症を克服することによって,クプロプトーシス介の抗腫瘍免疫反応を効果的に強化します.
- この戦略はエフェクターT細胞の活性化と増殖を促進し,長期的な抗がん免疫につながります.
関連する概念動画
Tumor Immunotherapy
523
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.
523
Cytotoxic T Cells-mediated Immune Response
907
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...
907
The Tumor Microenvironment
6.6K
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...
6.6K
Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
Cancer Therapies
7.7K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.7K
Tumor Progression
6.3K
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...
6.3K


