Figure 1.

The biological steps to achieve an effective immune response in NPC. This figure is based on the original cancer–immunity cycle proposed by Chen and Mellman. ¹³ The steps and factors affecting the response of ICIs are edited to reflect the specific immunobiology of NPC. The release of NPC-specific antigens (1) and their subsequent presentation by dendritic cells (DCs) and other antigen-presenting cells (APCs) (2), is followed by T-cell priming and activation (3), trafficking into tumors (4), tumor infiltration (5), and recognition and killing of tumor cells (6 and 7). Notable NPC-specific characteristics of this cycle favoring antitumor immunity include the release of NPC-specific antigens (including EBV-derived antigens and a large number of neoantigens), activated monocytes which could also be considered as a kind of APCs, promoting the trafficking of immune cells into tumors [via tumor inflammasomes, increased chemoattraction, notable interferon-α (IFN-α) and IFN-γ], dense infiltration of immune cells into tumors, high expression of inhibitory receptors, elevated cytotoxicity genes, and chemokine receptors. Conversely, antitumor immunity could be impeded by the loss of NPC-specific neoantigens, major histocompatibility complex protein (MHC) aberration, defective DCs or antigen-processing machinery components (APM) deficiency, high epithelial indoleamine 2,3-dioxygenase, abundant myeloid-derived suppressor cells (MDSC) or regulatory T-cells (Tregs), rich M2-type tumor-associated macrophages (TAMs), and several features typically associated with T-cell exhaustion.