Table 9.
Mechanism of primary and secondary resistance to checkpoint blocked.
| Primary Resistance | Reference | Secondary Resistance | Reference |
|---|---|---|---|
| Presence of inactivating mutations in JAK1, JAK2, and beta2-microglobulin (B2M) | [122] | Inactivating mutations in beta2-microglobulin (B2M) | [123] |
| Lower MHC-I expression | [124] | Increased PD-L2 expression on PD-L1 negative tumor cells | [125] |
| Overexpression of VEGF | [126] | PD-L1 up-regulation | [127] |
| Activation of PI3K/AKT, ALK/STAT3, and MEK/ERK/STAT1 signaling pathways | [128] | JAK1/2 mutation | [129] |
| TGF-β signaling pathway | [130] | ||
| Epithelial-mesenchymal transition (EMT) | [131] | ||
| Exhaustion of T cells | [132] | ||
| Increase in Tumor-associated macrophage and Myeloid-derived suppressor cells (MDSCs) | [133] |