Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Front Endocrinol (Lausanne). 2021 Oct 21;12:726448. doi: 10.3389/fendo.2021.726448. eCollection 2021.
Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas.
人类垂体腺瘤是最常见的颅内肿瘤之一。尽管大多数这些肿瘤是良性的,可以通过药物治疗或经蝶窦手术治疗,但这些肿瘤的一部分生长迅速、侵袭性强、复发且仍然是治疗难题。由于针对免疫检查点受体 PD-1 和 CLTA-4 的抗体现在已常规用于癌症治疗,因此我们定量检测了人类垂体腺瘤和正常垂体中编码 PD-1、CLTA-4 及其配体 PD-L1、PD-L2、CD80 和 CD86 的 mRNA 的表达,最终目的是利用免疫检查点疗法治疗侵袭性垂体腺瘤。与正常人类垂体相比,侵袭性垂体腺瘤中 PD-L2、CD80 和 CD86 的表达增加。此外,侵袭性垂体肿瘤中 CD80 和 CD86 的水平明显高于非侵袭性肿瘤。我们的研究结果为研究免疫检查点抑制治疗在垂体腺瘤治疗中的潜在作用提供了依据。