嗜铬细胞瘤和副神经节瘤中 SSTR2 和 HIF-2α的免疫组化特征及其与肿瘤微环境的关系

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.