Darragh Laurel B, Karam Sana D
Department of Immunology, University of Colorado Denver-Anschutz Medical Campus, Aurora, CO, USA.
Department of Radiation Oncology, University of Colorado Denver-Anschutz Medical Campus, Aurora, CO, USA.
Mol Carcinog. 2022 Feb;61(2):153-164. doi: 10.1002/mc.23354. Epub 2021 Sep 27.
Presentation of tumor antigens is a critical step in producing a robust antitumor immune response. Classically tumor antigens are thought to be presented to both CD8 and CD4 T cells by professional antigen-presenting cells (pAPCs) like dendritic cells using major histocompatibility complexes (MHC) I and II. But recent evidence suggests that in the tumor microenvironment (TME) cells other than pAPCs are capable of presenting tumor antigens on both MHC I and II. The evidence currently available on tumor antigen presentation by epithelial cells, vascular endothelial cells (VECs), fibroblasts, and cancer cells is reviewed herein. We refer to these cell types in the TME as "amateur" APCs (aAPCs). These aAPCs greatly outnumber pAPCs in the TME and could, potentially, play a significant role in priming an antitumor immune response. This new evidence supports a different perspective on antigen presentation and suggests new approaches that can be taken in designing immunotherapies to increase T cell priming.
肿瘤抗原的呈递是产生强大抗肿瘤免疫反应的关键步骤。传统上，肿瘤抗原被认为是由专职抗原呈递细胞（pAPC）如树突状细胞利用主要组织相容性复合体（MHC）I和II呈递给CD8和CD4 T细胞的。但最近的证据表明，在肿瘤微环境（TME）中，除pAPC外的其他细胞也能够在MHC I和II上呈递肿瘤抗原。本文综述了目前关于上皮细胞、血管内皮细胞（VEC）、成纤维细胞和癌细胞呈递肿瘤抗原的现有证据。我们将TME中的这些细胞类型称为“非专职”APC（aAPC）。这些aAPC在TME中的数量远远超过pAPC，并且可能在启动抗肿瘤免疫反应中发挥重要作用。这一新证据支持了对抗原呈递的不同观点，并提出了在设计免疫疗法以增加T细胞启动方面可以采用的新方法。
