研究动态
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T 细胞比例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.

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
来源: Cancers

摘要:

背景:免疫治疗显着提高了胸膜间皮瘤患者的总生存率,但这种益处并不适用于上皮样亚型患者。据信肿瘤生长受到免疫反应的影响。本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。方法:采用多重免疫荧光染色对188例胸膜间皮瘤患者的肿瘤免疫细胞浸润进行表征,包括CD3细胞(CD3 )、CD4细胞(CD3 /CD4 )、CD8细胞(CD3 /CD8 )、Treg细胞(CD3 /CD4 /CD8- )。 /CD163-/Foxp3)、PD1细胞(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:共分析了 188 例胸膜间皮瘤患者(135 例上皮样瘤、9 例肉瘤样瘤、44 例双相亚型)。中位年龄为 64.8 岁。上皮样亚型的总生存期明显长于非上皮样亚型 (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 细胞的高比例与超过 12 个月的显着更长的总生存期相关 (p = 0.015)。在多变量分析中,CD4 细胞与调节性 T 细胞的比率保留了对总体生存的显着影响。结论:间皮瘤中 T 细胞免疫浸润的明显差异与总生存期密切相关。因此,肿瘤微环境可以作为预后生物标志物的来源。
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.