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:NK Cells and Other Cytotoxic Innate Lymphocytes in Colorectal Cancer Progression and Metastasis.
NK Cells and Other Cytotoxic Innate Lymphocytes in Colorectal Cancer Progression and Metastasis.
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结直肠癌(CRC)是全球最常见的恶性肿瘤之一,也是癌症相关死亡的主要原因。尽管其发病机制和进展复杂,但CRC很好地体现了免疫环境如何决定疾病结局。细胞毒性淋巴细胞,包括CD8+ T细胞和自然杀伤(NK)细胞的存在,是CRC中相关的预后因素,并与更好的总生存期相关。与NK细胞一起,其他先天淋巴细胞,即先天淋巴细胞(ILCs),已在CRC患者活检组织和肠道癌小鼠模型中被发现,发挥促肿瘤和抗肿瘤双重活性。特别是,最近描述了若干具有细胞毒性功能的1型先天淋巴细胞(ILC1),小鼠中的证据表明NK细胞和ILC1在控制CRC转移中均发挥作用。在这篇综述中,我们概述了NK细胞的特征以及具有细胞毒性功能的先天淋巴细胞不断扩展的谱系。我们还评论了这些先天淋巴细胞在肠道癌进展至转移过程中已描述的和潜在的作用。最后,我们讨论了CRC中细胞毒性先天淋巴细胞功能调控分子机制的最新进展。
Colorectal cancer (CRC) is one of the most common malignancies and leading causes of cancer-related deaths worldwide. Despite its complex pathogenesis and progression, CRC represents a well-fitting example of how the immune contexture can dictate the disease outcome. The presence of cytotoxic lymphocytes, both CD8 + T cells and natural killer (NK) cells, represents a relevant prognostic factor in CRC and is associated with a better overall survival.
Together with NK cells, other innate lymphocytes, namely, innate lymphoid cells (ILCs), have been found both in biopsies of CRC patients and in murine models of intestinal cancer, playing both pro- and anti-tumor activities.
In particular, several type 1 innate lymphoid cells (ILC1) with cytotoxic functions have been recently described, and evidence in mice shows a role for both NK cells and ILC1 in controlling CRC metastasis. In this review, we provide an overview of the features of NK cells and the expanding spectrum of innate lymphocytes with cytotoxic functions.
We also comment on both the described and the potential roles these innate lymphocytes can play during the progression of intestinal cancer leading to metastasis.
Finally, we discuss recent advances in the molecular mechanisms underlying the functional regulation of cytotoxic innate lymphocytes in CRC.
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