相关实验视频

Updated: Jun 5, 2025

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

瘤微环境响应纳米粒子增强 IDO1 阻断通过重塑代谢性免疫抑制来改造免疫疗法

Mengna Wang^1,2, Yuhong Liu^1,2, Yanshi Li¹

¹Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|December 11, 2024

概括

这项研究开发了对TME敏感的纳米粒子 (HMP1G NPs),该纳米粒子结合了胺2,3-二氧化酶1 (IDO1) 抑制剂和氧化供体. 这些纳米粒子通过改善瘤代谢和减少免疫抑制来增强免疫检查点阻塞疗法.

科学领域:

生物医学工程生物医学工程
癌症研究癌症研究
纳米技术纳米技术

背景情况:

免疫检查点阻塞 (ICB) 疗法的有效性受到代谢失调的瘤微环境 (TME) 的限制.
在TME中介于印度列胺2,3-二氧化酶1 (IDO1) 的免疫抑制和金氨酸积累阻碍了抗瘤免疫力.
开发克服TME代谢功能障碍的策略对于改善癌症治疗至关重要.

研究的目的:

为增强ICB治疗开发对TME敏感的纳米粒子 (HMP1GNP).
研究通过纳米粒子输送的1-甲基三甲 (1-MT) 和S-酸盐 (GSNO) 的协同效应.
阐明HMP1GNP调节TME并提高抗瘤免疫力的机制.

主要方法:

制造对TME敏感的纳米颗粒 (HMP1G NP) 封装1-MT和GSNO.
纳米粒子药物释放和催化活性在对TME刺激 (H+,谷) 的反应中体外表征.
在小鼠乳腺癌模型中对HMP1G NP治疗的体内评估,评估抗瘤免疫力和存活率.

主要成果:

在TME条件下,HMP1GNP成功释放了Mn2+,GSNO和1-MT.
释放的Mn2+和GSNO产生了活性氧物种和氧化,与1-MT协同作用以抑制IDO1和降低金氨酸.
通过AHR/STAT3/IL-6信号通路,HMP1GNP降低了瘤细胞衍生的IDO1,改善了托代谢并减少了免疫抑制.
用HMP1GNP治疗在小鼠乳腺癌模型中显示出显著的抗瘤效果和改善的生存结果.

结论:

HMP1G NPs代表了一种新的纳米平台,用于克服与TME相关的代谢挑战.
通过纳米颗粒同时提供IDO1抑制剂和氧化捐赠剂可以提高ICB的疗效.
这种方法为开发更有效的抗瘤免疫疗法提供了一个有希望的策略.

关键词:

在KYN/TRP代谢过程中.化学疗法是一种化学疗法.免疫抑制是一种免疫抑制.类胺2,3-二氧化酶1 类胺2,3-二氧化酶1

更多相关视频

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

相关概念视频

Tumor Immunotherapy

Tumor Immunotherapy

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.

The Tumor Microenvironment

The Tumor Microenvironment

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...

Cancer Therapies

Cancer Therapies

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...