Spatial architecture of regulatory T-cells correlates with disease progression in patients with nasopharyngeal cancer

作者：Fengge Zhou, Gulidanna Shayan, Shiran Sun, Xiaodong Huang, Xuesong Chen, Kai Wang, Yuan Qu, Runye Wu, Ye Zhang, Qingfeng Liu, Jianghu Zhang, Jingwei Luo, Xinqi Shi, Yang Liu, Bin Liang, Ye‐Xiong Li, Jingbo Wang, Junlin Yi · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.1015283 · 被引用次数：20 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、Head and Neck Cancer Studies

Purpose This study aims to investigate the prognostic value of composition and spatial architecture of tumor-infiltrating lymphocytes (TILs) as well as PDL1 expression on TILs subpopulations in nasopharyngeal carcinoma (NPC). Methods A total of 121 patients with NPC were included and divided into two groups: favorable (n = 68) and unfavorable (n = 53). The archived tumor tissues of the included patients were retrieved, and a tissue microarray was constructed. The density and spatial distribution of TILs infiltration were analyzed using the multiplex fluorescent immunohistochemistry staining for CD3, CD4, CD8, Foxp3, cytokeratin (CK), PDL1, and 4′,6-diamidino-2-phenylindole (DAPI). The infiltration density of TILs subpopulations and PDL1 expression were compared between the two groups. The Gcross function was calculated to quantify the relative proximity of any two types of cells. The Cox proportional hazards regression model was used to identify factors associated with overall survival (OS) and disease-free survival (DFS). Results The densities of regulatory T-cells (Tregs), effector T-cells (Teffs), PDL1+ Tregs, and PDL1+ Teffs were significantly higher in patients with unfavorable outcomes. PDL1 expression on tumor cells (TCs) or overall TILs was not associated with survival. Multivariate analysis revealed that higher PDL1+ Tregs infiltration density was independently associated with inferior OS and DFS, whereas Tregs infiltration density was only a prognostic marker for DF...