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
英文原题:Cell therapy for brain tumors: The first 60 years.
Cell therapy for brain tumors: The first 60 years.
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原发性脑肿瘤仍是致死率最高的癌症之一,但免疫疗法有巨大潜力克服现行标准治疗的局限。自20世纪60年代末以来,早期临床试验不断探索细胞免疫疗法治疗脑肿瘤。约60年前的最初研究中,脑肿瘤患者接受非特异性白细胞、外周血单个核细胞(PBMC)和骨髓细胞输注。这些早期研究显示治疗安全,偶尔可获得持久抗肿瘤应答,尤其是在细胞疗法与常规治疗联合或作为初始治疗时。此后,细胞疗法依次发展为淋巴因子活化杀伤细胞(LAK)、TIL(肿瘤浸润淋巴细胞)、体外非特异性扩增或抗原特异性T细胞、自然杀伤(NK)细胞和嵌合抗原受体(CAR)T细胞。本历史综述总结脑肿瘤过继细胞疗法的临床经验,并回顾已发表临床研究的关键发现。
Primary brain tumors remain among the most lethal cancers, but immunotherapy holds immense potential to overcome limitations of current standard treatment modalities. Since the late 1960s, early-phase clinical trials have iteratively tested cellular immunotherapies for the treatment of brain tumors. Six decades ago, in the earliest studies, brain tumor patients were treated with infusions of nonspecific leukocytes, peripheral blood mononuclear cells (PBMCs), and bone marrow cells.
These earliest studies demonstrated safety and occasional durable antitumor responses, particularly when cell therapies were combined with conventional modalities or administered in the upfront setting.
These early cell therapy approaches were chronologically followed by lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TILs), ex vivo nonspecifically expanded and antigen-specific T cells, natural killer (NK) cells, and chimeric antigen receptor (CAR) T cells. In this historical review, we summarize the clinical experience with adoptive cell therapies for brain tumors and review key findings from published clinical studies.
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