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:Identification of a TIGIT-expressing CD8(+) T cell subset as a potential prognostic biomarker in colorectal cancer.
Identification of a TIGIT-expressing CD8(+) T cell subset as a potential prognostic biomarker in colorectal cancer.
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TIGIT 是 T 细胞和 NK 细胞上的抑制性免疫检查点受体,通过与恶性细胞或抗原提呈细胞上的配体结合介导免疫抑制效应。在结直肠癌(CRC)中,抗 PD-1 等免疫检查点抑制剂显示出治疗前景,但许多患者出现耐药或复发。因此,识别用于预测疾病进展和治疗反应的可靠免疫生物标志物至关重要。对 CRC 患者转录组数据的分析显示,TIGIT 高表达与较差的总生存期和无病生存期相关。TIGIT 表达还与免疫浸润相关,尤其是 CD8 + T 细胞。单细胞 RNA 测序鉴定出 CRC 患者中富集的一群独特的 TIGIT + PD-1 + CXCL13 + CD8 + T 细胞亚群。体外共培养实验证实,该表型由肿瘤细胞诱导,提示肿瘤驱动的 T 细胞功能障碍机制。该 TIGIT + PD-1 + CXCL13 + CD8 + T 细胞群体可能作为 CRC 预后和免疫治疗反应的潜在生物标志物。
TIGIT is an inhibitory immune checkpoint receptor on T cells and NK cells that mediates immunosuppressive effects by binding to ligands on malignant or antigen-presenting cells. In colorectal cancer (CRC), immune checkpoint inhibitors like anti-PD-1 show therapeutic promise, but many patients experience resistance or relapse.
Therefore, identifying robust immune biomarkers for predicting disease progression and therapeutic response is critical. Analysis of transcriptomic data from CRC patients revealed that high TIGIT expression is associated with poorer overall and disease-free survival. TIGIT expression also correlated with immune infiltration, particularly CD8 + T cells.
Single-cell RNA sequencing identified a distinct subset of TIGIT + PD-1 + CXCL13 + CD8 + T cells enriched in CRC patients. In vitro co-culture experiments confirmed that this phenotype is induced by tumor cells, suggesting a tumor-driven mechanism of T cell dysfunction. This TIGIT + PD-1 + CXCL13 + CD8 + T cell population may serve as a potential biomarker for prognosis and immunotherapy response in CRC.
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