T细胞比率对胸膜间皮瘤生存的影响：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
影响因子:4.40000
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
摘要
背景：免疫疗法在胸膜间皮瘤患者中的总体生存率显着提高，但是这种益处并未扩展到上皮类亚型的患者。据信肿瘤生长受到免疫反应的影响。这项研究旨在分析肿瘤微环境，以更好地了解其对肿瘤生长的影响。 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+),和T辅助细胞（CD3+/CD4+/CD8-/CD163-/FOXP3-）。特异性免疫细胞的分布与临床参数相关。结果：分析了总共188例胸皮瘤患者（135例上皮类，9例肉瘤，44个双相亚型）。中位年龄为64.8岁。上皮类亚型的总生存率明显长于非上皮类亚型的总生存期（p = 0.016）。 PD-L1表达的存在对总体存活率有负面影响（P = 0.041）。 CD4+细胞与调节T细胞的高比例与超过12个月以上的总体生存率明显更长（P = 0.015）有关。在多元分析中，CD4+细胞与调节T细胞的比率保持了其对总体存活的显着影响。结论：间皮瘤中T细胞免疫浸润的明显差异与总生存率密切相关。因此，肿瘤微环境可以作为预后生物标志物的来源。
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.