Department of Pathology, Johns Hopkins Hospital, School of Medicine, Baltimore, Maryland, USA.
Endocr Relat Cancer. 2023 Nov 22;31(1). doi: 10.1530/ERC-23-0196. Print 2024 Jan 1.
Cytotoxic T lymphocyte-associated protein 4 (CTLA4), a negative regulator typically expressed on the surface of T lymphocytes, is targeted by immunotherapy in patients with an ever-expanding spectrum of cancers. Characterizing the expression of CTLA4 in the pituitary gland could provide additional rationale for using immune checkpoint inhibitors in pituitary adenoma patients who do not respond to conventional treatments. We assessed the expression of CTLA4 mRNA and protein in a panel of 157 human pituitary glands, 45 collected at autopsy and 112 at surgery. These specimens included 50 normal glands and 107 adenomas: 41 nonsecreting, 25 PRL-, 24 ACTH-, 11 GH-, 2 TSH-, 1 FSH-secreting, and 3 atypical. Specimens were stained for CTLA4 and adenohypophyseal hormones using RNAscope in situ hybridization, immunohistochemistry, and RNAscope Multiplex Fluorescent Assay. CTLA4 mRNA was detectable in most normal pituitary glands (48 of 50, 96%) but varied in expression, with a histological score (H-score) ranging from 0.6 to 20. The variation did not depend upon the patient's gender and age and was not significantly affected by the archival storage time. CTLA4 expression was higher (P = 0.022) in pituitary adenomas than normal glands, with the greatest levels seen in PRL- and GH-secreting adenomas (P = 0.009 and 0.023 versus normal, respectively). Eight of 25 (32%) prolactinomas and 3 of 11 (27%) GH-adenomas had an H-score greater than 20, while no differences were seen for the other types. These novel data highlight the expression of an immune checkpoint such as CTLA4 on pituitary endocrine cells, a finding that could be exploited for therapeutical applications.
细胞毒性 T 淋巴细胞相关蛋白 4（CTLA4）是一种通常表达于 T 淋巴细胞表面的负性调节剂，在具有不断扩大的癌症谱的患者中，其是免疫治疗的靶点。描述 CTLA4 在垂体中的表达，可以为那些对常规治疗无反应的垂体腺瘤患者使用免疫检查点抑制剂提供更多的依据。我们评估了 157 个人类垂体组织标本中 CTLA4mRNA 和蛋白的表达情况，其中 45 例取自尸检，112 例取自手术。这些标本包括 50 例正常垂体和 107 例腺瘤：41 例无分泌功能，25 例分泌 PRL，24 例分泌 ACTH，11 例分泌 GH，2 例分泌 TSH，1 例分泌 FSH，3 例为不典型腺瘤。使用 RNAscope 原位杂交、免疫组织化学和 RNAscope 多重荧光检测法对 CTLA4 和腺垂体激素进行染色。大多数正常垂体（50 例中的 48 例，96%）中可检测到 CTLA4mRNA，但表达情况存在差异，组织学评分（H 评分）范围为 0.6 至 20。这种差异与患者的性别和年龄无关，也不受存档时间的显著影响。CTLA4 在垂体腺瘤中的表达（P = 0.022）高于正常垂体，在分泌 PRL 和 GH 的腺瘤中表达水平最高（分别与正常相比，P = 0.009 和 0.023）。25 例泌乳素瘤中有 8 例（32%）和 11 例 GH 腺瘤中有 3 例（27%）的 H 评分大于 20，而其他类型的腺瘤则无差异。这些新的数据强调了 CTLA4 等免疫检查点在垂体内分泌细胞上的表达，这一发现可能被用于治疗应用。
