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
探究微卫星稳定 RAS 突变结肠癌的免疫景观
英文原题：Interrogating the immune landscape of microsatellite stable RAS-mutated colon cancer.
查看英文原题
Interrogating the immune landscape of microsatellite stable RAS-mutated colon cancer.
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中文摘要
为了探索RAS突变（RASmt）微卫星稳定（MSS）结肠癌（CC）的免疫微环境，我们回顾性进行了全外显子测序、RNA测序和稳健的数字病理分析，并在一个队列中研究了免疫标志物，该队列包括161例接受标准治疗方案的早期疾病患者（新鲜冷冻和福尔马林固定石蜡包埋[FFPE]样本）或121例转移性患者（原发肿瘤FFPE样本）。只有一小部分病例表现出高度浸润的免疫微环境，其中Immunoscore ®（IS）高（占样本的13%）与肿瘤淋巴细胞浸润评分（TuLIS）高（占样本的25%）之间存在强关联。Immunoscore免疫检查点（ISIC）高肿瘤（占样本的52%）与IS高和TuLIS样高肿瘤具有相似的微环境组成，并且显示出比ISIC低肿瘤更高的突变负荷。总之，相当一部分MSS RASmt CC表现出高ISIC评分，值得在基于免疫治疗的联合方案的前瞻性试验中进行评估。
展开英文摘要原文
To explore the immune microenvironment of RAS-mutated (RASmt) microsatellite stable (MSS) colon cancer (CC), we retrospectively performed whole exome sequencing, RNA sequencing, and robust digital pathology analyses and studied immune markers in a cohort of 161 patients treated with standard-of-care therapies with early stage disease (both fresh frozen and formalin-fixed paraffin-embedded [FFPE] samples) or 121 patients with metastatic setting (primary tumor FFPE samples).
Only a small proportion of cases exhibited a highly infiltrated immune microenvironment, with a strong association between Immunoscore ® (IS)-high (13% of the samples) and Tumor Lymphocytes Infiltrating Score (TuLIS)-high scores (25% of the samples). Immunoscore Immune-Checkpoint (ISIC)-high tumors (52% of the samples) shared a similar microenvironment composition to IS-high and TuLIS-like high tumors and displayed higher mutational burdens than ISIC-low tumors.
In conclusion, a substantial proportion of MSS RASmt CCs exhibit high ISIC scores, meriting evaluation in prospective trials of immunotherapy-based combination regimens.
论文信息
- 作者
- Dienstmann R、García-Galea E、O'Farrell A、Kinsella Z、Meylan M、Petitprez F、Arijs I、Venken T
- 第一作者单位
- Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.Spain
- 通讯作者单位
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland.Ireland
- 文献类型
- 非美国政府资助研究
- 期刊
- Molecular oncology2026 Jul
- 原文标识
- PubMed 41733106 · DOI 10.1002/1878-0261.70225
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