Examining the spatial distribution of tumor-infiltrating immune cells in patients with stage I to IIIA LUAD
Examining the spatial distribution of tumor-infiltrating immune cells in patients with stage I to IIIA LUAD
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DOI：
10.1093/jleuko/qiae012
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发表时间：
2024-01-17
影响因子：
5.5
通讯作者：
Wei，Feng
中科院分区：
文献类型：
--
作者：
Du，Weijiao;Yang，Fan;Wei，Feng
本研究旨在应用Gcross函数检测170例I~IIIA期肺腺癌患者免疫细胞的空间分布，并探讨其预后价值。共有170例接受根治性手术的I-IIIA期LUAD患者入选。收集肿瘤石蜡切片进行多色免疫荧光染色(第1组：CD4、CD8、FOXP3、CD69、CD39、CD73、DAPI；第2组：CD68、CD163、CD20、CD11c、PDL1、IDO、DAPI)。免疫细胞分为CD8+、CD4+T辅助细胞(CD4Th)、调节性T细胞、巨噬细胞1型(M1)、M2、树突状细胞(DC)和B细胞。计数免疫细胞数，用Gcross函数计算免疫细胞贴近度。通过单因素COX回归分析探讨免疫细胞变量与无病生存率(DFS)的相关性。对有P<；0.05的因素进行多因素分析。单因素COX回归分析显示，pDL1+和pDL1+DC总数为阴性因素(P值分别为0.003和0.031)。CD4Th和IDO−DC计数为阳性因素(P分别为0.022和0.024)。单因素COX分析显示，邻近度评分(M1~M2)是影响DFS的积极因素(P=0.032)，而邻近度评分(PDL1+DC~M1)是影响DFS的负因素(P=0.009)。在多因素分析中，分期(IIIA vs I+II)(危险比：1.77[95%可信区间：1.18~2.64]，P=0.006)和邻近评分(PDL1+DC对M1)(HR：1.6[95%CI：1.07~2.37]，P=0.021)是独立的负面因素，CD4Th计数(HR：0.6[95%CI：0.40~0.9]，P=0.013)是独立的积极因素。我们的研究表明，较高水平的肿瘤浸润性CD4Th细胞预示着较长的DFS，而PDL1+DC更接近M1细胞与I-IIIA LUAD患者较差的DFS相关。
This study aimed to examine the spatial distribution of immune cells by application of Gcross function in 170 patients with stage I to IIIA lung adenocarcinoma (LUAD) and explore its prognostic value. A total of 170 stage I to IIIA LUAD patients who underwent radical surgery were enrolled. Paraffinized tumor sections were collected for 2 panels of multicolor immunofluorescence staining (panel 1: CD4, CD8, FOXP3, CD69, CD39, CD73, and DAPI; panel 2: CD68, CD163, CD20, CD11c, PDL1, IDO, and DAPI). The immune cells were categorized as CD8+, CD4+T helper cell (CD4Th), regulatory T cell, macrophage type 1 (M1), M2, dendritic cell (DC), and B cell. The immune cell numbers were enumerated, and the immune cell proximity score was calculated employing the Gcross function. The correlation between immune cell variables and disease-free survival (DFS) was explored through univariate Cox regression analyses. Factors withP< 0.05 were subjected to multivariate analyses. According to univariate Cox regression analyses, total PDL1+and PDL1+DC counts were negative factors (P =0.003 and 0.031, respectively). CD4Th and IDO−DC counts were positive factors (P =0.022 and 0.024, respectively). The proximity score (M1 to M2) was a positive factor for DFS (P= 0.032), and the proximity score (PDL1+DC to M1) was a negative factor (P= 0.009) according to univariate Cox analyses. In multivariate analyses, stage (IIIA vs I + II) (hazard ratio [HR]: 1.77 [95% confidence interval (CI): 1.18–2.64],P= 0.006) and proximity score (PDL1+DC to M1) (HR: 1.60 [95% CI: 1.07–2.37],P= 0.021) were independent negative factors and CD4Th counts (HR: 0.60 [95% CI: 0.40–0.90],P= 0.013) was an independent positive factor. Our study indicated that a higher level of tumor-infiltrating CD4Th cells predicted longer DFS, and a closer proximity of PDL1+DCs to M1 cells was associated with dismal DFS in stage I to IIIA LUAD patients.