肿瘤抗原的鉴定和表征是开发抗癌免疫疗法的中心目标。传统上，认为肿瘤相关抗原（TAAs）相对限于肿瘤细胞（即，在肿瘤细胞中过度表达的蛋白质），而肿瘤特异性抗原（TSAs）则认为是肿瘤细胞独有的。最近的研究聚焦于鉴定患者特异性新抗原，这些抗原可能高度免疫原性，因为它们在正常组织中并未表达。随着反调控T细胞（anti-Tregs）的发现，另一种策略也浮现出来，这些T细胞会攻击肿瘤微环境中的许多细胞类型，比如，调节性免疫细胞，而不仅仅是肿瘤细胞。本文建议使用“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，TMAs提供了几个与传统肿瘤抗原不同的优点。靶向TMAs不仅会直接攻击肿瘤细胞，还会调节肿瘤微环境，使其具备免疫能力并对肿瘤不友好。需要注意的是，与TAAs和TSAs相比，TMAs也在表达一致的人类白细胞抗原（HLA）的非转化细胞中。炎症常常会诱导恶性细胞表达HLA，因此针对TMAs的靶向治疗还可能影响表面HLA表达水平为零或极低的肿瘤。本文定义了TMAs的特征、差异和优点，并讨论了在免疫调节疫苗中使用这些抗原作为一种吸引人的免疫疗法方法的可能性。不同类型的TMAs由不同的细胞表达，可以在抗癌免疫疗法中组合使用，直接攻击肿瘤细胞并调节局部免疫细胞，以创造一个针对肿瘤不友好的微环境并抑制肿瘤血管生成。免疫调节疫苗提供了一种组合疗法的方法，包括检查点阻滞、细胞疗法或传统的癌症疫苗。这些组合疗法可以增加获益的患者数量，尤其是在炎症性肿瘤中具有最佳的效果。 © 2022. 作者。

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.© 2022. The Author(s).