肿瘤微环境抗原。

IF 7.9 2区 医学 Q1 IMMUNOLOGY Seminars in Immunopathology Pub Date : 2023-03-01 DOI:10.1007/s00281-022-00966-0
Mads Hald Andersen
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引用次数: 16

摘要

肿瘤抗原的鉴定和表征是发展抗癌免疫治疗的中心目标。传统上,肿瘤相关抗原(TAAs)被认为相对局限于肿瘤细胞(即肿瘤细胞中的过表达蛋白),而肿瘤特异性抗原(TSAs)被认为是肿瘤细胞所特有的。最近的研究集中在确定患者特异性的新抗原,这可能是高度免疫原性的,因为它们在正常组织中不表达。随着抗调节性T细胞(anti-Tregs)的发现,相反的策略已经出现,这些细胞除了肿瘤细胞外,还能识别和攻击肿瘤微环境中的许多细胞类型,如调节性免疫细胞。在这篇综述中提出的术语是“肿瘤微环境抗原”(TMAs)来描述引起这种攻击的抗原。作为治疗靶点,tma具有与传统肿瘤抗原不同的优势。靶向tma不仅可以直接攻击肿瘤细胞,还可以调节肿瘤微环境,使其具有免疫能力和肿瘤敌意。值得注意的是,与TAAs和tsa相比,TMAs也在具有一致的人类白细胞抗原(HLA)表达的非转化细胞中表达。炎症往往会诱导恶性细胞中HLA的表达,因此靶向TMAs可以额外影响表面HLA表达水平不高或极低的肿瘤。本文综述了TMAs与传统肿瘤抗原的特点、差异和优势,并讨论了这些抗原在免疫调节疫苗中的应用,作为一种有吸引力的免疫治疗方法。不同的tma由不同的细胞表达,可以联合用于抗癌免疫疗法,直接攻击肿瘤细胞,调节局部免疫细胞,形成肿瘤敌对微环境,抑制肿瘤血管生成。免疫调节疫苗提供了一种与其他免疫疗法(包括检查点阻断、细胞疗法或传统癌症疫苗)联合治疗的方法。这些组合将增加从这些治疗措施中受益的患者数量,这些治疗措施对炎症性肿瘤都有最佳的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Tumor microenvironment antigens.

The identification and characterization of tumor antigens are central objectives in developing anti-cancer immunotherapy. Traditionally, tumor-associated antigens (TAAs) are considered relatively restricted to tumor cells (i.e., overexpressed proteins in tumor cells), whereas tumor-specific antigens (TSAs) are considered unique to tumor cells. Recent studies have focused on identifying patient-specific neoantigens, which might be highly immunogenic because they are not expressed in normal tissues. The opposite strategy has emerged with the discovery of anti-regulatory T cells (anti-Tregs) that recognize and attack many cell types in the tumor microenvironment, such as regulatory immune cells, in addition to tumor cells. The term proposed in this review is "tumor microenvironment antigens" (TMAs) to describe the antigens that draw this attack. As therapeutic targets, TMAs offer several advantages that differentiate them from more traditional tumor antigens. Targeting TMAs leads not only to a direct attack on tumor cells but also to modulation of the tumor microenvironment, rendering it immunocompetent and tumor-hostile. Of note, in contrast to TAAs and TSAs, TMAs also are expressed in non-transformed cells with consistent human leukocyte antigen (HLA) expression. Inflammation often induces HLA expression in malignant cells, so that targeting TMAs could additionally affect tumors with no or very low levels of surface HLA expression. This review defines the characteristics, differences, and advantages of TMAs compared with traditional tumor antigens and discusses the use of these antigens in immune modulatory vaccines as an attractive approach to immunotherapy. Different TMAs are expressed by different cells and could be combined in anti-cancer immunotherapies to attack tumor cells directly and modulate local immune cells to create a tumor-hostile microenvironment and inhibit tumor angiogenesis. Immune modulatory vaccines offer an approach for combinatorial therapy with additional immunotherapy including checkpoint blockade, cellular therapy, or traditional cancer vaccines. These combinations would increase the number of patients who can benefit from such therapeutic measures, which all have optimal efficiency in inflamed tumors.

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来源期刊
Seminars in Immunopathology
Seminars in Immunopathology 医学-病理学
CiteScore
19.80
自引率
2.20%
发文量
69
审稿时长
12 months
期刊介绍: The aim of Seminars in Immunopathology is to bring clinicians and pathologists up-to-date on developments in the field of immunopathology.For this purpose topical issues will be organized usually with the help of a guest editor.Recent developments are summarized in review articles by authors who have personally contributed to the specific topic.
期刊最新文献
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