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胃癌中的肿瘤免疫反应与免疫治疗

Tumor immune response and immunotherapy in gastric cancer.

作者信息

Kwak Yoonjin, Seo An Na, Lee Hee Eun, Lee Hye Seung

机构信息

Department of Pathology, Seoul National University Hospital, Seoul, Korea.

Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

J Pathol Transl Med. 2020 Jan;54(1):20-33. doi: 10.4132/jptm.2019.10.08. Epub 2019 Nov 1.

Abstract

Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.

摘要

免疫肿瘤学的显著进展改变了胃癌(GC)的治疗格局。由于免疫疗法干预的是肿瘤免疫反应而非直接靶向肿瘤细胞,因此更深入地了解肿瘤免疫至关重要。本综述文章总结了肿瘤免疫反应和免疫逃逸机制,同时重点关注T细胞及其共抑制信号的作用,如免疫检查点分子程序性死亡蛋白1和程序性死亡配体1(PD-L1)。本文还描述了过去针对GC患者的免疫疗法临床试验,并详细阐述了其临床意义。强大的预测标志物对于提高免疫疗法的疗效至关重要。微卫星不稳定性、爱泼斯坦-巴尔病毒、PD-L1表达和肿瘤突变负荷现在被视为GC患者免疫疗法的有效预测标志物。有人提出了针对新的免疫检查点分子(如淋巴细胞激活基因3、T细胞免疫球蛋白和含粘蛋白结构域3)以及吲哚胺2,3-双加氧酶的新型免疫疗法和联合疗法,目前正在进行试验以评估其安全性和疗效。免疫疗法是GC患者的重要治疗选择,在改善患者预后方面具有巨大潜力,应在免疫肿瘤学领域开展进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8002/6986974/4399ae64963c/jptm-2019-10-08f1.jpg

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