Førde Dagny, Kilvær Thomas, Pedersen Mona Irene, Blix Egil S, Urbarova Ilona, Paulsen Erna-Elise, Rakaee Mehrdad, Busund Lill-Tove Rasmussen, Donnem Tom, Andersen Sigve
Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
Front Immunol. 2024 Dec 19;15:1504220. doi: 10.3389/fimmu.2024.1504220. eCollection 2024.
Tumor-infiltrating lymphocytes are both prognostic and predictive biomarkers for immunotherapy response. However, less is known about the survival benefits oftheir subpopulations.
Using machine learning models, we assessed the clinical association of the CD8+, PD1+, TCF1+ cel l subset by multiplex immunohistochemistry using tissue microarrays in 553 non-small cell lung cancer (NSCLC) patients and its correlation with other immune cell biomarkers.
We observed positive correlations between TCF1 and CD20 (r=0.37), CD3 (r=0.45)and CD4 (r=0.33). Notably, triple positive (CD8+PD1+TCF1+) were rare, only observed in 29 of 553 patients (5%). Our analysis revealed that cells coexpressing TCF1 with either CD8+ or PD1+ were independent prognostic markers of disease-specific survival in multivariable analysis (HR=0.728, p=0.029 for CD8+TCF1+, and HR=0.612, p=0.002 for PD1+TCF1+). To pilot the subtype of abundant CD8-TCF1+ cells, we explored an immune cell infiltrated whole slideimage and found the majority to be CD4+.
Overall, these findings suggest that assessment of CD8+, PD1+, TCF1+ could serve as a potential prognostic biomarker in NSCLC.
肿瘤浸润淋巴细胞既是免疫治疗反应的预后生物标志物，也是预测生物标志物。然而，对其亚群的生存益处了解较少。
我们使用机器学习模型，通过多重免疫组织化学方法，利用组织微阵列评估了553例非小细胞肺癌（NSCLC）患者中CD8 +、PD1 +、TCF1 +细胞亚群的临床关联及其与其他免疫细胞生物标志物的相关性。
我们观察到TCF1与CD20（r = 0.37）、CD3（r = 0.45）和CD4（r = 0.33）之间呈正相关。值得注意的是，三阳性（CD8 + PD1 + TCF1 +）细胞很少见，仅在553例患者中的29例（5%）中观察到。我们的分析显示，在多变量分析中，与CD8 +或PD1 +共表达TCF1的细胞是疾病特异性生存的独立预后标志物（CD8 + TCF1 +的HR = 0.728，p = 0.029；PD1 + TCF1 +的HR = 0.612，p = 0.002）。为了确定大量CD8 - TCF1 +细胞的亚型，我们探索了免疫细胞浸润的全切片图像，发现大多数为CD4 +。
总体而言，这些发现表明，评估CD8 +、PD1 +、TCF1 +可能作为NSCLC的潜在预后生物标志物。
