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
抗 VEGF 和抗 EGFR 抗体治疗对转移性结直肠癌中 T 细胞浸润和 TCR 变异的影响
英文原题：Anti-VEGF and Anti-EGFR Antibody Therapy on T-Cell Infiltration and TCR Variation in Metastatic Colorectal Cancer.
查看英文原题
Anti-VEGF and Anti-EGFR Antibody Therapy on T-Cell Infiltration and TCR Variation in Metastatic Colorectal Cancer.
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研究概要
抗 VEGF mAb 组中浸润肝转移灶的 T 细胞群体与抗 EGFR mAb 组不同。
研究思路结论见上方概要
背景
化疗联合抗EGFR或抗VEGF单克隆抗体（mAb）广泛用于治疗转移性结直肠癌（mCRC）患者。在此，我们研究了这些抗体对结直肠癌肝转移中T细胞浸润和T细胞受体（TCR）库变异的影响。
方法
10例mCRC患者接受了化疗联合抗EGFR（n=6）或抗VEGF（n=4）mAb治疗。通过免疫组化对治疗前后肝转移灶的活检或手术标本进行CD3和CD8检测，以评估T细胞浸润情况。对治疗后存在CD3+ T细胞浸润的标本进行了TCR库分析。
结果
抗EGFR mAb或抗VEGF mAb治疗后，T细胞浸润分别约为83%（5/6）和50%（2/4）。TCR repertoire分析显示，抗VEGF mAb组的TCR alpha和beta（TRA和TRB）克隆性更高、多样性更低，相比抗EGFR mAb组。此外，抗VEGF mAb组中浸润T细胞与外周血T细胞之间共有TCR克隆的百分比显著低于抗EGFR mAb组。
展开英文摘要原文
MATERIALS AND METHODS
Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3 + T-cell infiltration.
RESULTS
T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group.
CONCLUSION
The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group.
论文信息
- 作者
- Xu M、Tsunedomi R、Kiyotani K、Tomochika S、Furuya K、Nakajima M、Matsui H、Tokumitsu Y
- 第一作者单位
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.Japan
- 通讯作者单位
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan; hnagano@yamaguchi-u.ac.jp.Japan
- 期刊
- Anticancer research2023 Feb
- 原文标识
- PubMed 36697107 · DOI 10.21873/anticanres.16197