The necessary role of an efficient tumor immunotherapy by MHC II expression on amateur APCs

Abstract Antigen presentation, as the initial step in inducing the activation of T lymphocytes, plays a crucial role in antitumor response. Studies concentrating on major histocompatibility complex class II (MHC II) molecules and the activated CD4 + helper T (Th) cells have gained popularity in light of the past limited efficacy of MHC I‐activated CD8 + T cells alone. In general, MHC II is canonically expressed by professional antigen‐presenting cells (pAPCs), yet attempts to increase antigen presentation by dendritic cell (DC) activation have mostly been unsuccessful. In recent years, a number of studies have found that a variety of cells, including cancer cells, fibroblasts, vascular endothelial cells (VECs), and lymphoid stromal cells (LSCs), are considered amateur APCs (aAPCs) and can express MHC II molecules, which have piqued the interest of researchers. These groups vastly outnumber DCs or macrophages, and it has been confirmed that they also qualify as antigen‐presenting complexes that are functionally related to conventional pAPCs. Herein, we will review current research regarding the antigen presentation process of MHC II, its advances in APC surfaces, especially for aAPCs, the special mechanisms of regulation of MHC II on aAPCs, and combination therapy targeting MHC II as a possible treatment strategy in cancer.