Expression of B7-H3 and B7-H4 in Gastric Gastrointestinal Stromal Tumors.

IF 1.3 4区 医学 Q3 ANATOMY & MORPHOLOGY Applied Immunohistochemistry & Molecular Morphology Pub Date : 2024-11-01 Epub Date: 2024-10-02 DOI:10.1097/PAI.0000000000001227
Kunio Mochizuki, Naoki Oishi, Ippei Tahara, Tomohiro Inoue, Tetsuo Kondo
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Abstract

Gastric gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms with variable behavior characterized by differentiation toward the interstitial cells of Cajal occurring anywhere in the gastrointestinal stromal tract. The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first-line treatment for metastatic GIST. However, despite a clinical benefit rate of 80%, the majority of patients with GIST experience disease progression after 2 to 3 years of imatinib therapy. This shows the need for novel treatment approaches for imatinib refractory GISTs. The checkpoint proteins B7-H3 and B7-H4 inhibit the activation and function of T cells by potently suppressing the proliferation, cytokine production, and cytotoxicity of activated T cells, which is a mechanism for immune escape. This study aims to clarify B7-H3 and B7-H4 expression in gastric GISTs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). We confirmed B7-H3 expression (H-score ≥50 points) in 92% and B7-H4 expression in 0% of GIST samples. We examined B7-H3 mRNA expression in 3 representative GIST samples, each having their respective immunostained areas detected by RT-PCR. B7-H3 is expressed at a particularly high rate in GISTs. This suggests that B7-H3 might operate as part of an immune checkpoint in GISTs.

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胃肠道间质瘤中 B7-H3 和 B7-H4 的表达
胃肠道间质瘤(GIST)是一种间叶肿瘤,其特征是向卡贾尔间质细胞分化,发生在胃肠道间质的任何部位,表现各异。伊马替尼(一种 KIT 抑制剂)的问世彻底改变了 GIST 的治疗方法,它已成为转移性 GIST 的标准一线治疗药物。然而,尽管伊马替尼的临床获益率高达 80%,但大多数 GIST 患者在接受伊马替尼治疗 2 到 3 年后病情仍会恶化。这表明,伊马替尼难治性 GIST 需要新的治疗方法。检查点蛋白B7-H3和B7-H4通过有效抑制活化T细胞的增殖、细胞因子产生和细胞毒性来抑制T细胞的活化和功能,这是一种免疫逃逸机制。本研究旨在利用免疫组化和反转录聚合酶链反应(RT-PCR)明确胃癌 GIST 中 B7-H3 和 B7-H4 的表达。我们在 92% 的 GIST 样本中证实了 B7-H3 的表达(H 评分≥50 分),在 0% 的 GIST 样本中证实了 B7-H4 的表达。我们检测了 3 个具有代表性的 GIST 样本中 B7-H3 mRNA 的表达情况,每个样本都通过 RT-PCR 检测了各自的免疫染色区域。B7-H3 在 GIST 中的表达率特别高。这表明,B7-H3 可能是 GIST 中免疫检查点的一部分。
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来源期刊
Applied Immunohistochemistry & Molecular Morphology
Applied Immunohistochemistry & Molecular Morphology ANATOMY & MORPHOLOGY-MEDICAL LABORATORY TECHNOLOGY
CiteScore
3.20
自引率
0.00%
发文量
153
期刊介绍: ​Applied Immunohistochemistry & Molecular Morphology covers newly developed identification and detection technologies, and their applications in research and diagnosis for the applied immunohistochemist & molecular Morphologist. Official Journal of the International Society for Immunohistochemisty and Molecular Morphology​.
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