链接CD4+/CD8+T细胞新抗原疫苗接种克服了免疫检查点阻塞抵抗力,并使瘤回归成为可能
Joseph S Dolina1,2, Joey Lee1, Spencer E Brightman1
1Division of Developmental Immunology, La Jolla Institute for Immunology, La Jolla, California, USA.
The Journal of clinical investigation
|September 1, 2023
概括
使用链接新抗原 (NeoAg) 的组合免疫疗法可以在低TMB的瘤中克服对免疫检查点阻塞 (ICB) 的抵抗. 这种方法通过增强T细胞反应,扩大ICB可治疗的癌症来根除已建立的瘤.
科学领域:
- 免疫治疗是一种免疫疗法.
- 癌症研究 癌症研究
- 瘤微环境 瘤微环境
背景情况:
- 免疫检查点阻塞 (ICB) 的有效性在低瘤突变负担 (TMB) 的癌症中是有限的.
- T细胞对自发的新抗原 (NeoAg) 的识别对于ICB反应至关重要.
- 低TMB的瘤往往由于新抗原呈现不足而抵抗ICB.
研究的目的:
- 调查组合免疫疗法是否可以改善ICB响应在攻击性,低TMB状细胞瘤.
- 探索使用功能定义的NeoAg针对CD4+和CD8+T细胞.
- 评估与ICB结合的链接NeoAg疫苗的治疗潜力.
主要方法:
- 用单独或组合的CD4+或CD8+NeoAg接种疫苗.
- 在低TMB瘤模型中使用NeoAg疫苗和ICB的组合疗法.
- 对瘤微环境 (TME) 和T细胞状态 (耗尽,祖先) 的分析.
- 评估致癌干细胞 (tCSC) 和PD-L1表达.
主要成果:
- 针对CD4+和CD8+T细胞的NeoAg疫苗接种,具有物理联系的表位,克服了ICB耐药性.
- 组合疗法消除了大型,已建立的瘤,包括PD-L1+ tCSCs.
- 治疗性疫苗接种改变了TME,增加了NeoAg特异性的CD8+ T细胞在原始和中间疲状态.
- 通过ICB介导的分子间表位扩散增强了T细胞的反应.
结论:
- 与ICB结合的链接NeoAg疫苗接种是治疗低TMB瘤的有希望的策略.
- 这种方法可以克服ICB耐药性,并根除已建立的瘤.
- 基于这些原则的个性化癌症疫苗的进一步开发可以扩大ICB的适用性.
相关概念视频
01:27Tumor Immunotherapy
555
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.
555
01:27Cytotoxic T Cells-mediated Immune Response
963
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...
963
01:30Cancer Vaccines
400
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...
400
01:22T Cell Activation and Clonal Selection
804
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
804