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:Contribution of natural killer cells in innate immunity against colorectal cancer.
Contribution of natural killer cells in innate immunity against colorectal cancer.
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NK 细胞是先天免疫系统的成员,可不依赖主要组织相容性复合体(MHC)识别而对肿瘤细胞或感染细胞产生细胞毒作用。NK细胞受其活化/抑制受体表达调控,这些活化受体与抑制受体的比例决定NK细胞对靶细胞的细胞毒活性。由于NK细胞具有强效抗肿瘤特性,它们被视为肿瘤治疗的有吸引力策略。结直肠癌(CRC)是全球第二大癌症死亡原因,每年约新增200万病例。转移性CRC预后不佳,总生存期不足3年。化疗和手术是最常采用的治疗方式;此外,靶向治疗和免疫检查点阻断也是CRC治疗的新方法。在CRC患者中,循环NK细胞可作为预后标志物。CRC免疫细胞治疗的主要目标,是增强免疫细胞对肿瘤细胞的识别和清除能力;过继性NK细胞疗法是实现这一目标的重要途径。异体NK细胞疗法已在临床试验中得到广泛研究。本综述聚焦针对CRC肿瘤细胞的NK相关策略,包括CAR NK细胞、细胞疫苗、单克隆抗体和免疫调节药物。
Natural killer cells are members of the innate immune system and promote cytotoxic activity against tumor or infected cells independently from MHC recognition. NK cells are modulated by the expression of activator/inhibitory receptors. The ratio of this activator/inhibitory receptors is responsible for the cytotoxic activity of NK cells toward the target cells. Owing to the potent anti-tumor properties of NK cells, they are considered as interesting approach in tumor treatment. Colorectal cancer (CRC) is the second most common cause of death in the world and the incidence is about 2 million new cases per year. Metastatic CRC is accompanied by a poor prognosis with less than three years of overall survival.
Chemotherapy and surgery are the most adopted treatments. Besides, targeted therapy and immune checkpoint blockade are novel approach to CRC treatment. In these patients, circulating NK cells are a prognostic marker. The main target of CRC immune cell therapy is to improve the tumor cell's recognition and elimination by immune cells.
Adaptive NK cell therapy is the milestone to achieve the purpose. Allogeneic NK cell therapy has been widely investigated within clinical trials. In this review, we focus on the NK related approaches including CAR NK cells, cell-based vaccines, monoclonal antibodies and immunomodulatory drugs against CRC tumoral cells.
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