瘤和 stromal 两部分的亡决定了对基于免疫细胞死亡的免疫疗法的反应性
Winnie Fernando1, Jarama Clucas2, Alberto Rizzo1
1The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, Fulham Road, London, UK.
Nature communications
|March 6, 2026
概括
针对三阴性乳腺癌 (TNBC) 的免疫疗法显示出有前途. 由RIPK1驱动的细胞死亡与抗PD-1疗法相结合,通过参与瘤和树皮细胞,提供了持久的瘤控制和免疫记忆.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 免疫疗法,包括免疫检查点阻塞 (ICB),已推进癌症治疗,但在晚期三阴性乳腺癌 (TNBC) 中表现出有限的疗效.
- 持久的癌症控制不仅需要瘤细胞的消除,还需要免疫细胞死亡 (ICD) 来刺激抗瘤免疫力.
- 使用一种Brca1−/−p53−/−有机物衍生的TNBC模型,反映基底类瘤免疫景观.
研究的目的:
- 在TNBC中研究RIPK1驱动的ICD与抗PD-1疗法的协同效应.
- 阐明治疗反应背后的机制,重点关注瘤内在和 stromal necroptosis 的作用.
- 探索提高免疫疗法在免疫学上"冷"瘤的疗效的策略.
主要方法:
- 使用Brca1−/−p53−/−有机物衍生TNBC模型.
- 研究了RIPK1和MLKL操纵瘤和树皮细胞对治疗结果的影响.
- 评估了STING激动剂在使"冷"瘤对基于ICD的治疗产生反应方面的疗效.
主要成果:
- RIPK1驱动的ICD与抗PD-1疗法协同作用,在免疫透瘤中实现持久的瘤控制和免疫记忆.
- 瘤内在瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤瘤
- 刺痛激动剂使免疫学上"冷"的瘤对基于ICD的免疫疗法敏感.
结论:
- 将IAP对抗与检查点阻塞相结合的疗效严重依赖于瘤和树皮细胞的协调性亡.
- 整合瘤微环境环境对于设计TNBC有效的ICD向免疫疗法至关重要.
- 针对RIPK1驱动的ICD是一个有希望的策略,以克服先进的TNBC中对当前免疫疗法的耐药性.
相关概念视频
01:27Tumor 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
01:27Cytotoxic T Cells-mediated Immune Response
7.7K
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...
7.7K
01:30Overview of Cell Death
10.7K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
10.7K
01:16Necrosis
7.0K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
7.0K
02:17The Tumor Microenvironment
8.0K
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...
8.0K
01:17The Extrinsic Apoptotic Pathway
9.1K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.1K