免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Uveal melanoma: Recent advances in immunotherapy.
Uveal melanoma: Recent advances in immunotherapy.
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葡萄膜黑色素瘤(UM)是成人中最常见的原发性眼内恶性肿瘤。欧洲和美国的发病率为每年每百万人口6-7例。尽管大多数原发性UM可通过放射治疗或局部肿瘤切除术成功治疗并实现局部控制,但高达50%的UM患者会发生转移,通常累及肝脏,并在1年内致死。迄今为止,化疗和靶向治疗对转移性UM患者仅能获得极小的缓解,其预后仍然很差。目前尚未建立用于其预防或治疗的标准治疗方法。免疫治疗药物,如对皮肤黑色素瘤有效的免疫检查点抑制剂,在眼部疾病治疗中显示出有限的效果。这是由于UM具有独特的遗传学特征、自然病程以及与免疫系统的复杂相互作用。与主要以BRAF或NRAS突变为特征的皮肤黑色素瘤不同,UM通常由GNAQ或GNA11突变引发。
因此,目前正在研究更有效的免疫治疗方法,如癌症疫苗、过继性细胞转移和其他新分子。在这篇综述中,我们审视了临床和临床前研究中的新型免疫治疗策略,并重点介绍了免疫治疗的最新见解以及UM个体化治疗的发展。
Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established.
The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM's distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11.
As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.
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