间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Supervised machine learning to quantitatively assess the prognostic value of tumor-infiltrating lymphocytes in gastric cancer.
Supervised machine learning to quantitatively assess the prognostic value of tumor-infiltrating lymphocytes in gastric cancer.
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本研究建立了用于胃癌中 TIL 评估的定量工作流程。
随着对肿瘤免疫微环境认识不断深入,TIL(肿瘤浸润淋巴细胞)已成为抗肿瘤免疫的重要指标。多项研究显示其对胃癌(GC)具有预后价值。然而,人工或半定量评估TIL耗时且重复性较差。
依据TNM分期,将388例胃腺癌患者随机分层为训练队列和验证队列。研究者使用QuPath建立自动化流程,在苏木精—伊红(H&E)染色的组织芯片(TMA)明场图像中识别肿瘤细胞、TIL及其他基质细胞,并据此计算TIL相关变量。采用Kaplan-Meier分析、log-rank检验以及单变量和多变量Cox比例风险模型评估预后意义。研究构建了纳入年龄、T分期、淋巴结转移以及TIL占全部细胞比例(pTIL)的列线图,用于预测1年和3年总生存期(OS)。
两个队列中TIL水平较高均与OS改善相关。多变量分析证实,pTIL是OS的重要预后因素。列线图可有效预测1年及3年OS。值得注意的是,基于列线图的风险分层在区分低风险和中等风险患者方面,判别能力优于TNM分期。
本研究建立了用于GC的定量TIL评估流程。将TIL相关参数与临床特征相结合可增强风险分层,并可能改善个体化预后预测。
With growing insights into the tumor immune microenvironment, tumor-infiltrating lymphocytes (TILs) have emerged as key indicators of anti-tumor immunity. Numerous studies highlight their prognostic value in gastric cancer (GC). However, manual or semi-quantitative TIL assessment is time-consuming and poorly reproducible.
A total of 388 patients with gastric adenocarcinoma were randomly stratified into training and validation cohorts based on TNM stage. QuPath was used to establish an automated workflow for identifying tumor cells, TILs, and other stromal cells in brightfield hematoxylin-eosin (H&E)-stained tissue microarrays (TMAs). TIL-related variables were derived from these classifications. Prognostic significance was assessed using Kaplan-Meier analysis, log-rank tests, and univariable and multivariable Cox proportional hazards models. A nomogram incorporating age, T stage, lymph node metastasis and the proportion of TILs among all cells (pTILs) was built to predict 1- and 3-year overall survival (OS).
Higher levels of TILs were associated with improved OS in both cohorts. Multivariate analysis confirmed that pTILs was an important prognostic factor for OS. The nomogram effectively predicted 1-year and 3-year OS. Notably, the nomogram-based risk stratification demonstrated better discriminative ability than TNM stage in distinguishing between low- and middle-risk patients.
This study established a quantitative workflow for TIL assessment in GC. Integrating TIL-related parameters with clinical characteristics enhances risk stratification and may improve individualized prognosis prediction.
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