CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune microenvironment of medulloblastoma: The association between its molecular subgroups and potential targeted immunotherapeutic receptors.
Immune microenvironment of medulloblastoma: The association between its molecular subgroups and potential targeted immunotherapeutic receptors.
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髓母细胞瘤(MB)被认为是儿童中最常见的恶性脑肿瘤。包括手术、放疗和化疗在内的多模式治疗提高了患者的生存率。然而,30%的病例仍会出现复发。持续的死亡率、当前疗法未能延长预期寿命,以及非靶向细胞毒性治疗的严重并发症,均表明需要更精细的治疗方法。大多数MB起源于新小脑外表面的外颗粒层神经元,并负责传入和传出连接。近年来,MB已被分为四个分子亚组:Wingless激活型(WNT-MB)(第1组);Sonic-hedgehog激活型(SHH-MB)(第2组);第3组和第4组MB。这些分子改变遵循特定的基因突变和疾病风险分层。当前针对这些分子亚组的治疗方案和正在进行的临床试验仍在使用常规化疗药物,其疗效改善了无进展生存期,但未改变总生存期。
然而,探索针对MB微环境中特定受体的新疗法变得至关重要。MB的免疫微环境由独特的细胞异质性组成,包括免疫细胞和非免疫细胞。肿瘤相关巨噬细胞和TIL(肿瘤浸润淋巴细胞)被认为是肿瘤微环境中的主要细胞,其作用仍在研究中。在这篇综述中,我们讨论了MB细胞与微环境中免疫细胞之间相互作用的机制,并概述了近期研究和临床试验。
Medulloblastoma (MB) is considered the commonest malignant brain tumor in children. Multimodal treatments consisting of surgery, radiation, and chemotherapy have improved patients' survival. Nevertheless, the recurrence occurs in 30% of cases. The persistent mortality rates, the failure of current therapies to extend life expectancy, and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches. Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.
Recently, MBs have been segregated into four molecular subgroups: Wingless-activated (WNT-MB) (Group 1); Sonic-hedgehog-activated (SHH-MB) (Group 2); Group 3 and 4 MBs. These molecular alterations follow specific gene mutations and disease-risk stratifications. The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.
However, the need to explore new therapies targeting specific receptors in MB microenvironment became essential. The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.
Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment, and their role are still under investigation. In this review, we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment, with an overview of the recent investigations and clinical trials.
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