Table 1.
Determinants of immune exclusion.
| References | ||
|---|---|---|
| Mechanical barriers: physical impediments to a direct contact between T cells and cancer cells | ||
| ECM remodeling | Cancer-associated fibrosis | (42–48) |
| Epithelial-to mesenchymal transition | (49–55) | |
| Filaggrin, desmosomal proteins, endothelin B receptor | (30, 56–58) | |
| Vascular accessibility | HIF-1 and HIF-2 driven angiogenesis | (59–63) |
| Cancer cell coating | CXCL12 | (64–66) |
| Functional barriers: determinants limiting migration, function, and/or survival of T cells | ||
| Metabolic alterations TME | Decrease in amino acids in the TME | (67–72) |
| Warburg effect (increase in lactate) | (73–76) | |
| Increase in extracellular adenosine | (77–80) | |
| Increase in potassium | (62, 81, 82) | |
| Altered lipid metabolism | (83) | |
| Cyclooxygenase and prostaglandin metabolism | (84–86) | |
| Hypoxia | (87–91) | |
| Soluble factors | VEGF-α | (59, 60, 92–94) |
| Cytokines mediated immune suppressive mechanisms | (42, 43, 95–98) | |
| Danger sensing molecules | TAM receptors | (99–102) |
| don’t eat me signals | (103–105) | |
| Tolerogenic cell death/absent immunogenic cell death | (106–108) | |
| Tumor cell signaling | STAT-3, PI3K, NF-κB, Wnt/β-catenin, MAPK, p53 | (109–114) |
| Dynamic barriers: barriers arising after interaction between T cells and cancer cells | ||
| Checkpoint/ligand interactions | (39–41) | |