Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0–30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = −0.385,p= 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348,p= 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.
转移性嗜铬细胞瘤和副神经节瘤（PPGLs）是罕见的内分泌恶性肿瘤，目前有效治疗方案有限。肿瘤微环境（TME）与生长抑素受体2（SSTR2）及缺氧诱导因子-2α（HIF-2α）在PPGLs中的关联性，对于优化免疫治疗联合策略至关重要，但目前相关研究仍较为缺乏。为评估PPGLs患者中SSTR2和HIF-2α免疫反应性与TME的关联，我们通过免疫组化方法分析了PPGLs患者中SSTR2A、HIF-2α及TME组分（包括肿瘤浸润淋巴细胞CD4和CD8、肿瘤相关巨噬细胞CD68和CD163以及PD-L1）的表达情况。主要研究目标是确定免疫特征与SSTR2A和HIF-2α表达之间的关联。在45例PPGLs患者中，分别有21例（46.7%）和14例（31.1%）呈SSTR2A和HIF-2α阳性表达。PD-L1免疫组化评分中位数为2.0（四分位距：0-30.0）。CD4、CD8、CD68和CD163表达水平呈正相关。CD163/CD68比值（M2极化指标）与SSTR2A表达呈负相关（r = -0.385，p = 0.006）。HIF-2α表达与PD-L1评分呈正相关（r = 0.348，p = 0.013）。7例患者（15.6%）同时存在PD-L1（评分>10）与HIF-2α共表达。SDHB染色结果与CD163/CD68比值、PD-L1或SSTR2A表达均未显示相关性。本研究数据提示，在特定PPGLs人群中，免疫治疗联合肽受体放射性核素治疗或HIF-2α抑制剂可能成为潜在的治疗选择。
肿瘤(癌症)患者之家