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:Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma.
Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma.
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肾细胞癌(RCC)占所有成人癌症的2%-3%,是肾脏最常见的恶性肿瘤(90%)。上世纪九十年代中期,转移性RCC患者的标准治疗是细胞因子。舒尼替尼和帕唑帕尼分别于2007年和2009年获批,此后一直是转移性透明细胞RCC(mccRCC)的标准一线治疗。肾细胞癌是一种高度免疫原性肿瘤,具有肿瘤浸润细胞,包括CD8+ T淋巴细胞、树突状细胞、NK 细胞和巨噬细胞。这一观察结果促成了新的临床试验设计,在这些试验中患者接受免疫治疗。随着越来越多的证据表明促血管生成因子可对宿主免疫系统产生免疫调节作用,将血管生成药物与免疫治疗联合的想法应运而生,并设计了新的临床试验。在过去几年中,已有几种治疗选择获批[免疫治疗和免疫治疗/酪氨酸激酶抑制剂(TKI)]用于mccRCC的一线治疗。纳武利尤单抗/伊匹木单抗获批用于中危和低危预后患者的治疗。几种检查点抑制剂(帕博利珠单抗、纳武利尤单抗、阿维鲁单抗)联合TKI(阿昔替尼、仑伐替尼、卡博替尼)获批用于治疗患者,无论其国际mRCC数据库联盟预后分组和PD-L1表达如何。目前尚无特定且理想的生物标志物能够帮助选择适合接受适当一线治疗的理想患者。
Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy.
With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host's immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC.
Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.
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