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:A review on lymphocyte radiosensitivity and its impact on radiotherapy.
A review on lymphocyte radiosensitivity and its impact on radiotherapy.
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众所周知,放射治疗会导致患者淋巴细胞减少,且这与不良预后相关。其机制尚不明确,因为放射既具有免疫刺激作用,也具有免疫抑制作用。放射治疗中肿瘤剂量适形度、剂量分割方式以及选择性淋巴结照射如何影响淋巴细胞减少和免疫反应,是一个活跃的研究领域。
此外,理解放射对免疫系统的影响,对于设计和解读将放射与免疫检查点抑制剂联合使用的临床试验非常重要,无论是在放射剂量还是治疗方案方面。尽管循环中的淋巴细胞仅占淋巴细胞总数的百分之几,但有人推测其较高的放射敏感性可能促进、甚至可能是淋巴细胞减少的主要原因。本综述总结了基于人体、小动物和体外研究的淋巴细胞放射敏感性已发表数据。数据表明,不同淋巴细胞亚群之间的放射敏感性存在差异,这影响它们的相对贡献,从而影响免疫反应的动态变化。
总体而言,B 细胞似乎比 T 细胞更耐放射敏感,而 NK 细胞似乎最具抵抗性。然而,已报道的剂量-反应数据提示,在患者淋巴细胞减少的背景下,除细胞死亡之外的其他方面也必须加以考虑。不仅绝对淋巴细胞计数,淋巴细胞的多样性和活性也可能受到放射的影响。
综上所述,所综述的数据表明,放射诱导的淋巴细胞细胞死亡不太可能是放射诱导淋巴细胞减少的唯一因素。
It is well known that radiation therapy causes lymphopenia in patients and that this is correlated with a negative outcome. The mechanism is not well understood because radiation can have both immunostimulatory and immunosuppressive effects. How tumor dose conformation, dose fractionation, and selective lymph node irradiation in radiation therapy does affect lymphopenia and immune response is an active area of research.
In addition, understanding the impact of radiation on the immune system is important for the design and interpretation of clinical trials combining radiation with immune checkpoint inhibitors, both in terms of radiation dose and treatment schedules. Although only a few percent of the total lymphocyte population are circulating, it has been speculated that their increased radiosensitivity may contribute to, or even be the primary cause of, lymphopenia.
This review summarizes published data on lymphocyte radiosensitivity based on human, small animal, and in vitro studies. The data indicate differences in radiosensitivity among lymphocyte subpopulations that affect their relative contribution and thus the dynamics of the immune response. In general, B cells appear to be more radiosensitive than T cells and NK cells appear to be the most resistant.
However, the reported dose-response data suggest that in the context of lymphopenia in patients, aspects other than cell death must also be considered. Not only absolute lymphocyte counts, but also lymphocyte diversity and activity are likely to be affected by radiation. Taken together, the reviewed data suggest that it is unlikely that radiation-induced cell death in lymphocytes is the sole factor in radiation-induced lymphopenia.
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