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:CTL-NK Signature Based on Immune Gene Profiling and IHC Predicts Clinical Outcomes in Triple-Negative Breast Cancer.
CTL-NK Signature Based on Immune Gene Profiling and IHC Predicts Clinical Outcomes in Triple-Negative Breast Cancer.
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CTL 和 NK 浸润的定量和空间评估为 TNBC 提供了独立的预后信息。
三阴性乳腺癌(TNBC)缺乏靶向治疗,并表现出异质性结局。TIL(肿瘤浸润淋巴细胞)(TILs)是候选预后生物标志物,可反映肿瘤免疫微环境。本研究评估了细胞毒性T淋巴细胞(CTLs)和自然杀伤(NK)细胞在TNBC中的预后价值,重点关注颗粒溶素(GNLY)和颗粒酶B(GZMB)。材料与
我们在一个TNBC队列(n = 155)中,将NanoString免疫基因谱分析与全切片免疫组化(IHC)相结合。进行了定量和空间分析,以评估CTL和NK细胞浸润及其与临床病理特征和生存结局的关联。
高 TIL 密度(10%)和升高的 CTL-NK 评分(2)与较低肿瘤分期、无淋巴血管侵犯(LVI)以及有利的免疫亚群比值相关(所有 p < 0.05)。在多变量分析中,无 LVI、高 CD4 + 和 CD8 + 浸润以及 CTL-NK 评分 2 独立预测改善的无病生存期(DFS;风险比 [HR] 范围 0.45-0.62,所有 p < 0.05)。CD4 + 浸润显示出最强的预后效应,而 CD8 + 浸润和 CTL-NK 评分也带来了独立获益。
We combined NanoString immune gene profiling with whole-slide immunohistochemistry (IHC) in a TNBC cohort ( n = 155). Quantitative and spatial analyses were performed to assess CTL and NK cell infiltration and their associations with clinicopathological features and survival outcomes.
High TIL density ( 10%) and elevated CTL-NK scores ( 2) correlated with lower tumor stage, absence of lymphovascular invasion (LVI), and favorable immune subset ratios (all p < 0.05). In multivariable analysis, absence of LVI, high CD4 + and CD8 + infiltration, and CTL-NK score 2 independently predicted improved disease-free survival (DFS; hazard ratio [HR] range 0.45-0.62, all p < 0.05). CD4 + infiltration demonstrated the strongest prognostic effect, while CD8 + infiltration and the CTL-NK score also conferred independent benefit.
Quantitative and spatial assessment of CTL and NK infiltration provides independent prognostic information in TNBC. The CTL-NK score can be integrated into routine pathology and may refine risk stratification, supporting personalized immunotherapy strategies. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted treatments and often has poorer outcomes compared with other subtypes. Immune cells within the tumor, called tumor-infiltrating lymphocytes (TILs), can influence how the cancer behaves and how patients respond to treatment. In this study, we looked closely at two types of immune cells cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells and the proteins they use to destroy cancer cells, granulysin (GNLY) and granzyme B (GZMB). Using both immune gene testing and special staining of tumor samples, we measured how many of these cells were present and where they were located in the tumor. We found that patients whose tumors had higher CTL and NK cell activity lived longer without the cancer returning. We created a simple CTL NK score that could help doctors predict outcomes in TNBC and identify patients who may benefit most from immunotherapy.
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