Matsumura Eiji, Kajino Kazunori, Abe Masaaki, Ohtsuji Naomi, Saeki Harumi, Hlaing May Thinzar, Hino Okio
Departments of Pathology and Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Oncology Medical Science, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Pathol Int. 2020 Dec;70(12):999-1008. doi: 10.1111/pin.13028. Epub 2020 Oct 7.
Mesothelioma is a rare, aggressive malignancy with poor outcome, and has limited treatment options. The aim of this study was to perform a comprehensive analysis of programmed death ligand 1 (PD-L1) and B7 homolog 3 (B7-H3) expression in mesothelioma. We investigated the protein expression of PD-L1 and B7-H3 and their potential correlation with histological subtype, which might help to develop new therapies targeting these immune checkpoint molecules. Expression analysis of PD-L1 and B7-H3 was performed by immunohistochemistry using serial tissue sections of specimens obtained from 31 patients with mesothelioma. Tumors were classified into 22 epithelioid, 6 sarcomatoid, and 3 biphasic types. Of the 31 patients, 13 (41.9%) were positive for PD-L1 and 28 (90.3%) were B7-H3 positive. Twelve of the 13 PD-L1 positive patients were positive for B7-H3. PD-L1 and B7-H3 were widely co-expressed in biphasic and sarcomatoid type tumor cells. These findings might provide a rationale for the use of combination therapy for mesothelioma by targeting PD-L1 and B7-H3, as well as the development of anti-B7-H3 or anti-PD-L1 single agents.
间皮瘤是一种罕见的侵袭性恶性肿瘤,预后较差,治疗选择有限。本研究的目的是对间皮瘤中程序性死亡配体1(PD-L1)和B7同源物3(B7-H3)的表达进行全面分析。我们研究了PD-L1和B7-H3的蛋白表达及其与组织学亚型的潜在相关性,这可能有助于开发针对这些免疫检查点分子的新疗法。使用从31例间皮瘤患者获得的标本的连续组织切片,通过免疫组织化学进行PD-L1和B7-H3的表达分析。肿瘤分为22例上皮样、6例肉瘤样和3例双向型。在31例患者中,13例(41.9%)PD-L1阳性,28例(90.3%)B7-H3阳性。13例PD-L1阳性患者中有12例B7-H3阳性。PD-L1和B7-H3在双向型和肉瘤样型肿瘤细胞中广泛共表达。这些发现可能为通过靶向PD-L1和B7-H3对间皮瘤进行联合治疗以及开发抗B7-H3或抗PD-L1单药提供理论依据。