通过向TGF-β信号阻断在TH细胞中的癌症免疫疗法
Shun Li1, Ming Liu1, Mytrang H Do1,2
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|October 22, 2020
概括
向转化生长因子β (TGF-β) 在CD4+T细胞中,重塑瘤微环境,增强癌症免疫力. 这种方法抑制了瘤的生长,
科学领域:
- 免疫学
- 癌症学
- 癌症生物学
背景情况:
- 针对瘤细胞或血管内皮生长因子A (VEGFA) 的癌症疗法通常会遇到抗药性.
- 已知转化生长因子-β (TGF-β) 抑制了T助手2 (TH2) 细胞介导的抗癌免疫力.
- 现有的治疗方法有局限性,需要针对瘤微环境的新疗法.
研究的目的:
- 研究阻断TGF-β信号的治疗潜力,特别是在CD4+T细胞内.
- 在T辅助细胞中开发和评估针对TGF-β阻断的新型双特异性分子.
- 评估这种向封锁对瘤进展和瘤微环境的影响.
主要方法:
- 使用一种对常规疗法的抗乳腺癌小鼠模型.
- 设计了一种双特异性分子,CD4 TGF-β Trap (4T-Trap),将TGF-β受体II (TGFBR2) 与抗CD4抗体结合起来.
- 用于评估4T-Trap对TH细胞TGF-β信号传递,瘤血管和癌细胞死亡的影响.
主要成果:
- 在抗性乳腺癌模型中,TGFBR2在CD4+T细胞中的诱导性删除抑制了瘤生长.
- 在瘤排水淋巴结中选择性抑制TH细胞TGF-β信号传递.
- 这种抑制导致了瘤血管的重组,依赖于IL-4的癌细胞死亡,以及瘤缺氧.
- 结合VEGF抑制与4T-Trap增强了癌细胞死亡和抗瘤作用.
结论:
- 在CD4+T细胞中向阻断TGF-β信号是重塑瘤微环境的可行策略.
- 这种方法通过增强抗瘤免疫力有效抑制癌症的进展.
- 设计的4T-Trap分子显示出开发针对瘤环境的新型癌症疗法的潜力.
相关概念视频
Tumor Immunotherapy
1.2K
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.
1.2K
Targeted Cancer Therapies
8.3K
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...
8.3K
Combination Therapies and Personalized Medicine
5.7K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.7K
Cancer Vaccines
801
Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
801
Mitogens and the Cell Cycle
7.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.5K
TGF - β Signaling Pathway
9.8K
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...
9.8K


