С细胞毒性T淋巴细胞相关蛋白-4(CTLA4)在分泌催乳素和生长激素的垂体腺瘤亚群中过表达。

Endocrine-related cancer Pub Date : 2023-11-22 Print Date: 2024-01-01 DOI:10.1530/ERC-23-0196
Elena Sabini, Amna Khan, Patrizio Caturegli
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引用次数: 0

摘要

CTLA4是一种通常在T淋巴细胞表面表达的负调节因子,是癌症谱系不断扩大的患者的免疫疗法靶向。对CTLA4在垂体中的表达进行表征,可以为在对传统治疗没有反应的垂体腺瘤患者中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个不分泌,25个PRL-,24个ACTH-,11个GH,2个TSH-,1个FSH分泌,3个非典型。使用RNAscope原位杂交、免疫组织化学和RNAscope多重荧光测定对标本进行CTLA4和腺垂体激素染色。CTLA4mRNA在大多数正常垂体中可检测到(48/50.96%),但表达不同,组织学评分(H评分)在0.6至20之间。变异不取决于患者的性别和年龄,也不受档案存储时间的影响。CTLA4在垂体腺瘤中的表达高于正常腺体(p=0.022),其中PRL和GH分泌腺瘤的表达水平最高(分别与正常腺体相比p=0.009和0.023)。25例泌乳素腺瘤中有8例(32%)和11例GH腺瘤中有3例(27%)的H核大于20,而其他类型的H核没有差异。这些新数据强调了免疫检查点如CTLA4在垂体内分泌细胞上的表达,这一发现可用于治疗应用。
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Сytotoxic T lymphocyte-associated protein 4 (CTLA4) is overexpressed in a subset of prolactin- and growth hormone-secreting pituitary adenomas.

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.

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