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) 是一种通常在 T 淋巴细胞表面表达的负调节因子，是癌症患者免疫治疗的目标。表征 CTLA4 在垂体中的表达可以为对传统治疗无反应的垂体腺瘤患者使用免疫检查点抑制剂提供额外的理由。我们评估了 157 个人类垂体中 CTLA4 mRNA 和蛋白质的表达，其中 45 个在尸检时收集，112 个在手术时收集。这些标本包括 50 个正常腺体和 107 个腺瘤：41 个非分泌腺体、25 个 PRL-、24 个 ACTH-、11 个 GH-、2 个 TSH-、1 个 FSH 分泌型和 3 个非典型腺瘤。使用 RNAscope原位杂交、免疫组织化学和 RNAscope 多重荧光测定对样本进行 CTLA4 和腺垂体激素染色。CTLA4 mRNA 在大多数正常垂体中均可检测到（50 例中的​​ 48 例，96%），但表达有所不同，组织学评分（H 评分）范围为 0.6 至 20。这种变化不取决于患者的性别和年龄，而是受档案保存时间影响不大。垂体腺瘤中的CTLA4 表达高于 正常腺体( P = 0.022)，其中在 PRL 和 GH 分泌腺瘤中表达水平最高（ 与正常腺瘤相比，分别为P = 0.009 和 0.023）。25 例泌乳素瘤中的 8 例 (32%) 和 11 例 GH 腺瘤中的 3 例 (27%) H 评分大于 20，而其他类型没有差异。这些新数据强调了垂体内分泌细胞上 CTLA4 等免疫检查点的表达，这一发现可用于治疗应用。