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
FFCD 1709-SIRTCI II 期试验：选择性内放射治疗联合 Xelox、贝伐珠单抗和阿替利珠单抗治疗以肝转移为主的转移性结直肠癌
英文原题：FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer.
查看英文原题
FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer.
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中文摘要
免疫检查点抑制剂（ICI）在具有微卫星不稳定性（MSI）的转移性结直肠癌（mCRC）中具有高效力，但在微卫星稳定（MSS）肿瘤中则不然，这是由于肿瘤突变负荷较低。选择性内放射治疗（SIRT）可以增强新抗原的产生，从而触发全身性抗肿瘤免疫反应（远隔效应）。
此外，奥沙利铂可以诱导免疫原性细胞死亡，贝伐珠单抗可以减少TIL（肿瘤浸润淋巴细胞）的耗竭。联合使用时，这些治疗可能协同作用，使MSS mCRC对ICI敏感。SIRTCI是一项前瞻性、多中心、开放标签、II期、非比较性单臂研究，评估SIRT联合Xelox、贝伐珠单抗和阿替利珠单抗（抗程序性死亡配体1）在肝脏为主的MSS mCRC患者中的疗效和安全性。主要目标是9个月时的无进展生存期。主要纳入标准为MSS mCRC患者，以肝脏为主，初始不可切除，且既往未接受过针对转移性疾病的肿瘤治疗。该试验于2020年11月开始，已纳入52例计划患者中的10例。
展开英文摘要原文
Immune checkpoint inhibitors (ICI) have high efficacy in metastatic colorectal cancer (mCRC) with microsatellite instability (MSI) but not in microsatellite stable (MSS) tumour due to the low tumour mutational burden. Selective internal radiation therapy (SIRT) could enhance neoantigen production thus triggering systemic anti-tumoral immune response (abscopal effect).
In addition, Oxalipatin can induce immunogenic cell death and Bevacizumab can decrease the exhaustion of tumour infiltrating lymphocyte. In combination, these treatments could act synergistically to sensitize MSS mCRCs to ICI SIRTCI is a prospective, multicentre, open-label, phase II, non-comparative single-arm study evaluating the efficacy and safety of SIRT plus Xelox, Bevacizumab and Atezolizumab (anti-programmed death-ligand 1) in patients with liver-dominant MSS mCRC.
The primary objective is progression-free survival at 9 months. The main inclusion criteria are patients with MSS mCRC with liver-dominant disease, initially unresectable disease and with no prior oncologic treatment for metastatic disease. The trial started in November 2020 and has included 10 out of the 52 planned patients.
论文信息
- 作者
- Randrian V、Pernot S、Le Malicot K、Catena V、Baumgaertner I、Tacher V、Forestier J、Hautefeuille V
- 第一作者单位
- Service d'Hépato-gastroentérologie, CHU de Poitiers et Université de Poitiers, Poitiers 86021, France.France
- 通讯作者单位
- Service d'Hépato-gastroentérologie, CHU de Poitiers et Université de Poitiers, Poitiers 86021, France. Electronic address: david.tougeron@chu-poitiers.fr.France
- 文献类型
- II 期临床试验 · 多中心研究
- 期刊
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver2022 Jul
- 原文标识
- PubMed 35610167 · DOI 10.1016/j.dld.2022.04.024