胸膜间皮瘤中T细胞比例对生存的影响：肿瘤微环境分析的见解

Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis

Cancers

影响因子:4.4

分区:医学3区 / 肿瘤学3区

发表日期:2024 Oct 08

作者: Laura V Klotz, Andreas Weigert, Florian Eichhorn, Michael Allgäuer, Thomas Muley, Rajiv Shah, Rajkumar Savai, Martin E Eichhorn, Hauke Winter

DOI: 10.3390/cancers16193418

摘要

背景：免疫治疗显著提高了胸膜间皮瘤患者的总生存期，但这一益处未能延伸至上皮型亚型。肿瘤生长被认为受到免疫反应的影响。该研究旨在通过分析肿瘤微环境，更好地理解其对肿瘤生长的影响。方法：采用多重免疫荧光染色，分析了188例胸膜间皮瘤患者的肿瘤免疫细胞浸润情况，包括CD3+细胞（CD3+）、CD4+细胞（CD3+/CD4+）、CD8+细胞（CD3+/CD8+）、调节性T细胞（Treg，CD3+/CD4+/CD8-/CD163-/Foxp3+）、PD1+细胞（PD1+）以及T辅助细胞（CD3+/CD4+/CD8-/CD163-/FoxP3-）。将特定免疫细胞的分布与临床参数相关联。结果：共分析了188例胸膜间皮瘤患者（其中上皮型135例，肉瘤样9例，双相44例），平均年龄为64.8岁。总体生存期在上皮型组明显长于非上皮型（p=0.016）。PD-L1表达的存在对总生存期有负面影响（p=0.041）。CD4+细胞与调节性T细胞的比例较高与超过12个月的显著更长的总生存期相关（p=0.015）。多变量分析中，该比例仍对总生存期具有显著影响。结论：间皮瘤中T细胞免疫浸润的差异与总生存期密切相关，肿瘤微环境可能作为预后生物标志物的重要来源。

Abstract

Background: Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth. Methods: The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters. Results: A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (p = 0.016). The presence of PD-L1 expression had a negative effect on overall survival (p = 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (p = 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis. Conclusions: Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.