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SLFN11 表达与免疫微环境相关并预测黑色素瘤预后

英文原题:SLFN11 expression correlates with immune microenvironment and predicts prognosis in melanoma.

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SLFN11 expression correlates with immune microenvironment and predicts prognosis in melanoma.

PubMed 2025/09/22(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

这些发现提供证据表明,SLFN11 与黑色素瘤的免疫微环境变化相关,与良好预后相关,并可能与免疫治疗反应有关,支持其作为进一步研究的候选生物标志物和治疗靶点的潜力。

研究思路结论见上方概要

Schlafen家族成员11(SLFN11)已被认为与癌症生物学和免疫调节有关,但其在黑色素瘤中的表达模式、预后价值及在肿瘤免疫中的作用仍未完全明确。

通过对公共数据库(The Human Protein Atlas、TIMER2、BEST)的多组学分析和功能验证,我们表征了SLFN11在黑色素瘤中的作用。在SLFN11过表达的黑色素瘤细胞中进行功能实验,以评估其对M0巨噬细胞极化、巨噬细胞和CD8⁺ T细胞募集以及CD8⁺ T细胞细胞毒性活性的影响。

SLFN11 mRNA水平在皮肤黑色素瘤(SKCM)中较正常皮肤降低,但在转移性病灶中高于原发性肿瘤。SLFN11高表达与多个独立黑色素瘤队列中有利的总生存期和无进展生存期相关,且在临床亚组(肿瘤分期、淋巴结/转移状态)中具有一致的预后价值。多变量Cox回归分析在调整性别、年龄和病理T/N/M分期等因素后,证实SLFN11表达是有利总生存期的独立预测因子。SLFN11表达与免疫细胞浸润增强以及免疫检查点分子的共表达相关。此外,SLFN11表达与接受免疫治疗患者的有利预后相关。功能实验显示,过表达SLFN11的黑色素瘤细胞促进M0巨噬细胞向M1表型极化,增强巨噬细胞和CD8⁺ T细胞的募集,并轻度增加CD8⁺ T细胞的细胞毒性活性。

展开英文摘要原文

Schlafen family member 11 (SLFN11) has been implicated in cancer biology and immune modulation, but its expression patterns, prognostic value, and role in tumor immunity in melanoma remain incompletely defined.

Through multi-omics analyses of public databases (The Human Protein Atlas, TIMER2, BEST) and functional validation, we characterized SLFN11 in melanoma. Functional assays were conducted in SLFN11-overexpressing melanoma cells to evaluate effects on M0 macrophage polarization, recruitment of macrophages and CD8⁺ T cells, and CD8⁺ T cell cytotoxic activity.

SLFN11 mRNA levels are reduced in skin cutaneous melanoma (SKCM) compared to normal skin, yet higher in metastatic lesions than in primary tumors. High SLFN11 expression correlates with favorable overall and progression-free survival across multiple independent melanoma cohorts, with consistent prognostic value across clinical subgroups (tumor stages, nodal/metastatic status). Multivariable Cox regression analysis, adjusting for factors like gender, age, and pathologic T/N/M stages, confirmed SLFN11 expression as an independent predictor of favorable overall survival. SLFN11 expression associates with enhanced infiltration of immune cells along with co-expression of immune checkpoint molecules. Furthermore, SLFN11 expression is associated with favorable prognosis in immunotherapy-treated patients. Functional assays show that SLFN11-overexpressing melanoma cells promote M0 macrophage polarization toward an M1 phenotype, enhance recruitment of macrophages and CD8⁺ T cells, and slightly increase CD8⁺ T cell cytotoxic activity.

These findings provide evidence that SLFN11 is associated with immune microenvironment changes in melanoma, correlates with favorable prognosis, and may be linked to immunotherapy response, supporting its potential as a candidate biomarker and therapeutic target for further investigation.

论文信息

作者
Zeng H、Chen G、Fang Y、Wu J、Jiang Q、Zhang R
单位
Department of Breast Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.China
期刊
Frontiers in immunology2025
原文标识
PubMed 41058684 · DOI 10.3389/fimmu.2025.1607056