组合免疫疗法改善了复制-修复-缺陷 (RRD) 高度质瘤失败的反PD-1单疗法的结果:国际RRD联盟的报告
Anirban Das1,2,3,4,5, Nicholas R Fernandez2,3, Adrian Levine6,7
1Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada.
Cancer discovery
|October 12, 2023
概括
免疫检查点抑制剂 (ICI) 对复制-修复-缺陷,高等级质瘤 (RRD-HGG) 显示出希望. 拯救疗法,包括再辐射和向药物,可以在这些超突变瘤中延长初始ICI失败后的生存期.
科学领域:
- 神经瘤学神经瘤学
- 免疫治疗是一种免疫疗法.
- 基因组学就是基因组学.
背景情况:
- 免疫检查点抑制 (ICI) 是对复制-修复-缺陷,高度质瘤 (RRD-HGG) 的一种公认的治疗方法.
- 在RRD-HGG中ICI单疗失败后,免疫导向策略的有效性仍然在很大程度上未被探索.
研究的目的:
- 研究免疫导向救援疗法的临床和生物影响,在RRD-HGG患者中,这些患者在ICI单一治疗中进展.
- 识别预测生物标志物,并了解不断发展的瘤免疫微环境.
主要方法:
- 一项针对75名RRD-HGG患者进行的国际回顾性研究,这些患者接受了抗PD-1疗法.
- 对接受基于ICI的救援,再辐射,CTLA4抑制或RAS-MAPK通路抑制的患者的结局分析.
- 评估基因组,转录组和免疫微环境的变化.
主要成果:
- 在第二次进展后继续基于ICI的救援疗法将整体存活时间延长到11.6个月 (n=38).
- 具有极端突变负担的患者在救援ICI (P=0.03) 时表现出更好的生存率.
- 重辐射反应与缺少有害的后辐射印记有关;CTLA4抑制和RAS-MAPK通路抑制显示出有希望的反应 (分别为75%和疗效).
结论:
- 超突变RRD-HGG可以从检查点抑制剂中获益,超过最初的进展.
- 重辐射和协同免疫/向剂可以通过利用独特的,不断发展的生物和免疫特性来改善RRD-HGG的生存率.
- 未来的研究应该专注于组合疗法,以最大限度地提高生存率并最大限度地降低免疫毒性.
更多相关视频
06:15Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
27.4K
11:15Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
8.0K
相关概念视频
01:27Tumor Immunotherapy
539
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.
539
02:56Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
02:50Combination Therapies and Personalized Medicine
4.9K
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...
4.9K