Figure 1. Factors controlling CD8 T-cell presence in tumors.

The infiltration of CD8 T-cells into tumors is controlled by many factors. Initial naïve T-cell (TN) priming to tumor antigens may be limited by poor tumor antigenicity or poor dendritic cell (DC) trafficking/maturation. If a large population of effector CD8 T-cells (TEff) is generated by spontaneous priming to tumor antigens, vaccination, or adoptive transfer, additional barriers may prevent the infiltration of these cells into the tumor. The tumor vasculature can express low levels of cognate ligands for the homing receptors expressed on the CD8 T-cell surface, or express ligands for homing receptors not expressed by the T-cells. High levels of VEGF produced by tumor and stromal cells such as tumor-associated macrophages (TAM) promote dysregulated angiogenesis, generating vasculature with abnormal mechanical properties that poorly supports CD8 T-cell infiltration. Activated T-cells that overcome these barriers and extravasate into the tumor can be suppressed by the tumor and other stromal populations, including regulatory T-cells (TReg) and myeloid-derived suppressor cells (MDSC). This limits their expression of inflammatory cytokines and inhibits further induction of ligand expression on the tumor vasculature.