Table 6 Underlying mechanisms of resistance to immunotherapy
Findings | Tumor type | N | Immunotherapy | Impact | References |
|---|---|---|---|---|---|
LOH in β2M | Metastatic melanoma | 160 | Ipilimumab, Pembrolizumab | No response | [188] |
Deficient IFN-γ pathway genes (IFNGR1, IRF1, JAK2 and IFNGR2) | Melanoma | 16 | Ipilimumab | No response | [177] |
Loss-of-function mutations in JAK1/2, inactivation of β2M | Metastatic melanoma | 4 | Pembrolizumab | Initial response followed by progression | [176] |
Gain-of-function mutations in β-catenin | Metastatic melanoma | 266 | anti-PD-L1/anti-CTLA-4 | Absence of T cell infiltration | [184] |
Active β-catenin expression | Melanoma model | – | ACT | No response, resistant to memory CD8 + T Cells | [186] |
Biallelic losses of β2M and HLA genes, upregulated WNT/β-catenin signaling | CRC | 179 | – | Absence of T cell infiltration | [7] |
Increased Wnt signaling, decreased IFN-γ levels | Melanoma | 31 | – | Suppression of induction and effector phases of anti-tumor T cell responses | [185] |
Loss-of-function mutations in JAK1/2 | Melanoma | 169 | Anti-PD-L1/anti-CTLA-4 | Progressive disease | [9] |
Loss-of-function mutations in JAK1/2 | Metastatic melanoma, CC | 39 | Anti-PD-1 | No response | [180] |