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
纳米颗粒 Toll 样受体 9 激动剂增强抗 Glypican-1 抗体的抗肿瘤活性
英文原题：Nano-particulate Toll-like Receptor 9 Agonist Potentiates the Antitumor Activity of Anti-Glypican-1 Antibody.
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Nano-particulate Toll-like Receptor 9 Agonist Potentiates the Antitumor Activity of Anti-Glypican-1 Antibody.
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研究概要
K3-SPG 与抗 GPC1 mAb 或其他抗肿瘤 mAb 的联合治疗可能代表一种通过 ADCC 发挥作用的新癌症治疗选择。
研究思路结论见上方概要
背景
靶向肿瘤抗原的单克隆抗体（mAbs）近年来已被开发出来。其抗肿瘤活性主要通过抗体依赖性细胞介导的细胞毒性（ADCC）实现，依赖于肿瘤浸润巨噬细胞和自然杀伤（NK）细胞等效应细胞。CpG寡脱氧核苷酸（ODNs）具有强效抗肿瘤活性，并被认为可增加巨噬细胞和NK细胞的肿瘤浸润；然而，一种完全溶解的新型CpG-裂褶多糖（SPG）复合物K3-SPG显示出更强的抗肿瘤活性。我们最近报道了抗glypican-1（GPC1）mAb通过ADCC对GPC1阳性食管鳞状细胞癌（ESCC）具有显著抗肿瘤活性。本研究旨在评估抗GPC1 mAb与K3-SPG的潜在协同抗肿瘤活性，并利用GPC1阳性人ESCC细胞的异种移植模型阐明其潜在机制。
方法
将已建立的人食管癌细胞系TE14皮下注射到SCID小鼠体内。对异种移植小鼠使用抗GPC1 mAb、K3-SPG或其联合方案进行治疗。通过测量肿瘤体积评估抗肿瘤活性。对于FACS分析，给予药物，并在最后一次治疗后1天切除肿瘤。
结果
抗GPC1 mAb或K3-SPG单药治疗显示出剂量依赖性的抗肿瘤活性，而抗GPC1 mAb与K3-SPG联合治疗显示出抗肿瘤活性（p=0.0859）。流式细胞术显示，K3-SPG或联合治疗后，巨噬细胞数量（p=0.0133）以及活化NK细胞/总NK细胞比值（p=0.0058）显著增加。
展开英文摘要原文
MATERIALS AND METHODS
The established human esophageal cancer cell line TE14 was subcutaneously injected into SCID mice. Xenograft mice were treated with anti-GPC1 mAb, K3-SPG, or their combination. Antitumor activity was evaluated by measuring the tumor volume. For FACS analysis, agents were administrated, and tumors were resected 1 day after the final treatment.
RESULTS
Anti-GPC1 mAb or K3-SPG monotherapy showed dose-dependent antitumor activity, and combination therapy with anti-GPC1 mAb and K3-SPG showed antitumor activity (p=0.0859). Flow cytometry revealed significantly increased numbers of macrophages (p=0.0133) and of the ratio of activated NK cells/total NK cells (p=0.0058) following K3-SPG or combination therapy.
CONCLUSION
Combination therapy with K3-SPG and anti-GPC1 mAb or another antitumor mAb may represent a new cancer treatment option acting via ADCC.
论文信息
- 作者
- Saito Y、Takahashi T、Hiramatsu K、Serada S、Fujimoto M、Ohkawara T、Sugase T、Nishigaki T
- 第一作者单位
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.Japan
- 通讯作者单位
- Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan; tnaka@iwate-med.ac.jp.Japan
- 期刊
- Anticancer research2023 Jun
- 原文标识
- PubMed 37247902 · DOI 10.21873/anticanres.16410