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:Natural killer cell awakening: unleash cancer-immunity cycle against glioblastoma.
Natural killer cell awakening: unleash cancer-immunity cycle against glioblastoma.
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由于忽视了复杂的肿瘤免疫微环境,胶质母细胞瘤的传统治疗在过去十年已达到局限,疗效仍不理想。基于癌症免疫循环理论的免疫治疗为胶质母细胞瘤患者带来新希望。然而,多数II期和III期临床试验结果并不乐观,原因可能是过于关注T细胞活化,而忽略了参与抗肿瘤免疫的其他免疫细胞。NK细胞在先天和适应性免疫中均发挥关键作用,能够协调炎症、自身免疫性疾病和癌症中的免疫应答。NK细胞有望与T细胞协同,最大限度增强抗肿瘤效应,在胶质母细胞瘤治疗中具有很大潜力。本文介绍胶质母细胞瘤的传统治疗方法和当前免疫治疗策略,绘制微环境图谱,并从多个角度探讨胶质母细胞瘤免疫抑制的原因。更重要的是,我们聚焦NK细胞作为潜在免疫调节细胞的优势,以及增强其抗肿瘤效应的方法。最后,我们展望结合先进技术的NK细胞疗法的方向和潜在应用。本综述将NK细胞唤醒视为释放抗癌免疫循环的前提,并从生物学机制到临床治疗阐述这一观点。
Due to the negligence of the complex tumor immune microenvironment, traditional treatment for glioblastoma has reached its limitation and cannot achieve a satisfying outcome in the past decade. The emergence of immunotherapy based on the theory of cancer-immunity cycle has brought a new dawn to glioblastoma patients.
However, the results of most phase II and phase III clinical trials are not optimistic due to the simple focus on T cells activation rather than other immune cells involved in anti-tumor immunity. NK cells play a critical role in both innate and adaptive immunity, having the ability to coordinate immune response in inflammation, autoimmune disease and cancer. They are expected to cooperate with T cells to maximize the anti-tumor immune effect and have great potential in treating glioblastoma.
Here, we describe the traditional treatment methods and current immunotherapy strategies for glioblastoma. Then, we list a microenvironment map and discuss the reasons for glioblastoma inhibitory immunity from multiple perspectives. More importantly, we focus on the advantages of NK cells as potential immune regulatory cells and the ways to maximize their anti-tumor immune effect.
Finally, our outlook on the directions and potential applications of NK cell-based therapy combining with the advance technologies is presented. This review depicts NK cell awakening as the precondition to unleash the cancer-immunity cycle against glioblastoma and elaborate this idea from biology to clinical treatment.
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