Nonfunctioning pituitary adenoma is a common intracranial tumor. Though benign in the majority of cases, complications can be excruciating to the affected individual, and recurrences after tumor removal may happen with more aggressive clinical features. T regulatory (Treg) cells are generally considered a tumor-promoting immune cell type in malignant cancers with currently unclear roles in pituitary adenoma patients. Therefore, we investigated the frequency and functional characteristics of Treg cells in nonfunctioning pituitary adenoma patients before and after tumor removal. Compared to healthy controls, untreated patients with nonfunctioning pituitary adenomas presented an overrepresentation of highly functional circulating FOXP3⁺ Treg cells. Specifically, the FOXP3⁺ Treg cells in patients were slightly upregulated in frequency and displayed markedly elevated capacity to co-produce TGF-β and IL-10. TIM-3 is a negative regulator of proinflammatory immune responses and is expressed by highly activated Treg cells. In both healthy controls and pituitary adenoma patients, TIM-3⁺ Treg cells presented significantly higher levels of TGF-β and IL-10 co-producing cells than TIM-3⁻ Treg cells but compared to healthy controls, patients with nonfunctioning pituitary adenomas showed significantly higher levels of TIM-3⁺ FOXP3⁺ Treg cells. Interestingly, surgical removal of the tumor significantly reduced the extent of Treg upregulation in patients. Also, resected pituitary adenomas contained highly functional FOXP3⁺ Treg cells, with high levels of TIM-3 expression and high frequency of TGF-β and IL-10 co-producers in the TIM-3⁺ fraction. Overall, these results demonstrate that patients with nonfunctioning pituitary adenomas are characterized by an overrepresentation of highly functional Treg cells.

无功能的垂体腺瘤是常见的颅内肿瘤。尽管在大多数情况下是良性的，但并发症可能使受影响的人难以忍受，并且肿瘤切除后的复发可能会以更具侵略性的临床特征发生。T调节（Treg）细胞通常被认为是恶性肿瘤中促进肿瘤的免疫细胞类型，目前在垂体腺瘤患者中的作用尚不清楚。因此，我们调查了肿瘤切除前后无功能的垂体腺瘤患者中Treg细胞的频率和功能特征。与健康对照相比，未经治疗的垂体腺瘤功能不全的患者过度表达了高功能循环FOXP3 ⁺ Treg细胞。具体来说，FOXP3 ⁺患者的Treg细胞的频率略有上调，并显示出联合产生TGF-β和IL-10的能力明显提高。TIM-3是促炎免疫反应的负调节剂，由高度活化的Treg细胞表达。在健康对照者和垂体腺瘤患者中，TIM-3 ⁺ Treg细胞的TGF-β和IL-10共生成细胞水平均显着高于TIM-3 ⁻ Treg细胞，但与健康对照者相比，垂体腺瘤无功能的患者表现出TIM-3 ⁺ FOXP3 ^+的含量明显更高Treg细胞。有趣的是，手术切除肿瘤显着降低了患者中Treg上调的程度。此外，切除的垂体腺瘤包含功能强大的FOXP3 ⁺ Treg细胞，在TIM-3 ⁺级分中具有高水平的TIM-3表达以及高频率的TGF-β和IL-10联合产生。总体而言，这些结果表明垂体腺瘤无功能的患者的特征是高功能性Treg细胞的过度表达。