文章：

肾上腺皮质癌中类固醇表型分层揭示不同的HLA表达特征

Steroid Phenotype Stratification Reveals Distinct HLA Expression Signatures in Adrenocortical Carcinoma

原文发布日期：12 January 2026

DOI: 10.3390/cancers18020229

类型: Article

开放获取: 是

英文摘要：

Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy where endogenous steroid excess may foster immune evasion. However, whether this hormonal axis directly modulates the antigen presentation machinery remains unclear.Methods: We applied an immunoinformatics approach to the TCGA-ACC cohort (n= 79) to investigate relationships among steroid phenotype, HLA expression, tumor microenvironment (TME), and patient outcome. Key findings were assessed in an independent validation cohort (ENSAT-ACC,n= 44) using C1A/C1B molecular subtypes corresponding to the steroid phenotypes.Results: Stratification by steroid phenotype revealed two distinct immunological profiles. The high steroid production (HSP) phenotype was associated with suppressed HLA expression and a lymphocyte-depleted “cold” TME. In contrast, the low steroid production (LSP) phenotype displayed elevated HLA expression, enriched T-cell infiltration, and upregulation of immune checkpoints (e.g., PDCD1, CTLA4), consistent with an inflamed but exhausted TME. The core signature of HLA downregulation in the HSP-like phenotype (C1A) and the significant survival advantage of the LSP-like phenotype (C1B) were confirmed in the validation cohort, demonstrating biological robustness despite platform and sample size differences.Conclusions: These findings identify the steroid phenotype as a critical regulator of immune escape in ACC. Our results support incorporating this stratification as a biomarker for patient selection, identifying LSP tumors as the subgroup most likely to benefit from immune checkpoint blockade due to their “hot” yet exhausted microenvironment.

摘要翻译： 

背景：肾上腺皮质癌（ACC）是一种罕见且具有侵袭性的恶性肿瘤，其内源性类固醇过量可能促进免疫逃逸。然而，该激素轴是否直接调控抗原呈递机制尚不明确。

方法：我们对TCGA-ACC队列（n=79）应用免疫信息学方法，研究类固醇表型、HLA表达、肿瘤微环境（TME）与患者预后之间的关系。关键发现在独立验证队列（ENSAT-ACC，n=44）中通过对应类固醇表型的C1A/C1B分子亚型进行评估。

结果：根据类固醇表型分层，揭示了两种不同的免疫特征。高类固醇生成（HSP）表型与HLA表达抑制以及淋巴细胞缺失的“冷”TME相关。相反，低类固醇生成（LSP）表型显示出HLA表达升高、T细胞浸润增多以及免疫检查点（如PDCD1、CTLA4）上调，符合一种炎症性但耗竭的TME特征。在验证队列中，HSP样表型（C1A）中HLA下调的核心特征以及LSP样表型（C1B）显著的生存优势得到了证实，表明尽管平台和样本量存在差异，但生物学结果具有稳健性。

结论：这些发现确定了类固醇表型是ACC中免疫逃逸的关键调节因子。我们的结果支持将这种分层作为一种生物标志物用于患者筛选，由于LSP肿瘤具有“热”但耗竭的微环境，它们是最可能从免疫检查点阻断疗法中获益的亚组。

原文链接：

Steroid Phenotype Stratification Reveals Distinct HLA Expression Signatures in Adrenocortical Carcinoma