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实体瘤中的 LAG3 作为一种潜在的新型免疫治疗靶点。

LAG3 in Solid Tumors as a Potential Novel Immunotherapy Target.

机构信息

Department of Medicine, Division of Hematology-Oncology.

Department of Internal Medicine, Division of Hematology-Oncology, Ewha Woman's University College of Medicine, Seoul, Korea.

出版信息

J Immunother. 2019 Oct;42(8):279-283. doi: 10.1097/CJI.0000000000000283.

Abstract

We performed a prospective immunohistochemical analysis of lymphocyte activation gene 3 (LAG3) for 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Most patients (428/430, 99.5%) were evaluable for LAG3 expression by immunohistochemistry. In total, 18.5% (79/428) of the evaluated cancers expressed LAG3, including pancreatic cancer (33.3%, 2/6), gastric cancer (24.7%, 21/85), colorectal cancer (23.6%, 48/203), melanoma (12.5%, 1/8), genitourinary cancer (9.5%, 4/46), biliary tract cancer (6.3%, 1/16), and sarcoma (5.4%, 2/37), but not miscellaneous (0.0%, 0/14) or hepatocellular (0.0%, 0/15) cancer. Among 149 metastatic colorectal cancer patients, there was no statistically significant difference in sex, age, primary tumor site, pathologic differentiation, KRAS and NRAS status, BRAF status, and microsatellite instability according to LAG3 status (expressed vs. nonexpressed). Among 53 metastatic gastric cancer patients, LAG3 was only significantly associated with Epstein Barr virus status (P=0.042). Our results add to the emerging literature on LAG3 expression in various cancer types and support the need for extended clinical exploration of this target for immunotherapy.

摘要

我们对 2012 年 6 月至 2016 年 3 月间的 430 例晚期胃肠道、泌尿生殖系统或罕见癌症患者进行了淋巴细胞激活基因 3(LAG3)的前瞻性免疫组化分析。通过免疫组化评估,大多数患者(428/430,99.5%)可评估 LAG3 的表达。在评估的癌症中,总共有 18.5%(79/428)表达 LAG3,包括胰腺癌(33.3%,2/6)、胃癌(24.7%,21/85)、结直肠癌(23.6%,48/203)、黑色素瘤(12.5%,1/8)、泌尿生殖系统癌(9.5%,4/46)、胆管癌(6.3%,1/16)和肉瘤(5.4%,2/37),但非其他类型(0.0%,0/14)或肝细胞癌(0.0%,0/15)。在 149 例转移性结直肠癌患者中,根据 LAG3 状态(表达与不表达),性别、年龄、原发肿瘤部位、病理分化、KRAS 和 NRAS 状态、BRAF 状态和微卫星不稳定性无统计学差异。在 53 例转移性胃癌患者中,仅 EBV 状态与 LAG3 显著相关(P=0.042)。我们的研究结果增加了关于 LAG3 在各种癌症类型中表达的文献,并支持对该免疫治疗靶点进行进一步的临床探索。

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