RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
神经母细胞瘤中的免疫检查点分子：临床视角
英文原题：Immune checkpoint molecules in neuroblastoma: A clinical perspective.
查看英文原题
Immune checkpoint molecules in neuroblastoma: A clinical perspective.
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中文摘要
高危神经母细胞瘤（NB）的治疗具有挑战性，患者的5年长期生存率仍低于50%，且肿瘤复发或再发后生存机会较低。目前正在测试或评估不同的策略，以消灭耐药肿瘤并改善NB患者的生存结局。免疫疗法利用人体免疫系统的某些部分来识别或杀死肿瘤细胞，可有效改善包括NB在内的多种癌症患者的结局。免疫治疗策略之一是阻断肿瘤中的免疫检查点信号，以增加肿瘤免疫原性和抗肿瘤免疫。免疫检查点蛋白对免疫细胞功能施加刹车以调节免疫激活，但肿瘤利用这种活性来逃避免疫监视和攻击。免疫检查点蛋白在NB生物学和免疫逃逸机制中发挥重要作用，这使这些肿瘤在免疫上呈“冷”状态。阻断免疫检查点信号的治疗策略在NB中已显示出有希望的结果，但仅见于一部分患者。
然而，将免疫检查点阻断与其他疗法联合，包括基于偶联抗体的免疫治疗、放射免疫治疗、肿瘤疫苗或细胞疗法如修饰T细胞或自然杀伤（NK）细胞，已在临床前环境中显示出增强抗肿瘤免疫的令人鼓舞的结果。使用计算工具对公开可用数据集进行的分析揭示了包括NB在内的多种癌症的复杂性。本综述全面总结了当前关于免疫检查点分子、其生物学特性、在免疫抑制和肿瘤发展中的作用，以及将免疫检查点抑制剂与其他疗法联合以对抗高危NB的新型治疗策略的信息。
展开英文摘要原文
High-risk neuroblastoma (NB) is challenging to treat with 5-year long-term survival in patients remaining below 50% and low chances of survival after tumor relapse or recurrence. Different strategies are being tested or under evaluation to destroy resistant tumors and improve survival outcomes in NB patients. Immunotherapy, which uses certain parts of a person's immune system to recognize or kill tumor cells, effectively improves patient outcomes in several types of cancer, including NB.
One of the immunotherapy strategies is to block immune checkpoint signaling in tumors to increase tumor immunogenicity and anti-tumor immunity. Immune checkpoint proteins put brakes on immune cell functions to regulate immune activation, but this activity is exploited in tumors to evade immune surveillance and attack.
Immune checkpoint proteins play an essential role in NB biology and immune escape mechanisms, which makes these tumors immunologically cold. Therapeutic strategies to block immune checkpoint signaling have shown promising outcomes in NB but only in a subset of patients.
However, combining immune checkpoint blockade with other therapies, including conjugated antibody-based immunotherapy, radioimmunotherapy, tumor vaccines, or cellular therapies like modified T or natural killer (NK) cells, has shown encouraging results in enhancing anti-tumor immunity in the preclinical setting.
An analysis of publicly available dataset using computational tools has unraveled the complexity of multiple cancer including NB. This review comprehensively summarizes the current information on immune checkpoint molecules, their biology, role in immune suppression and tumor development, and novel therapeutic approaches combining immune checkpoint inhibitors with other therapies to combat high-risk NB.
论文信息
- 作者
- Pathania AS、Prathipati P、Murakonda SP、Murakonda AB、Srivastava A、Avadhesh、Byrareddy SN、Coulter DW
- 第一作者单位
- Department of Biochemistry and Molecular Biology & The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.United States
- 通讯作者单位
- Department of Biochemistry and Molecular Biology & The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; The Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: kishore.challagundla@unmc.edu.United States
- 文献类型
- 综述 · 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Seminars in cancer biology2022 Nov
- 原文标识
- PubMed 35787940 · DOI 10.1016/j.semcancer.2022.06.013