Amateur antigen-presenting cells in the tumor microenvironment

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.