Tumor immune evasion strategies
| . | Defects . | Immune cell-based therapies . | Combinations with immune cell–based therapies . |
|---|---|---|---|
| Tumor-associated DC dysfunction | Reduced DC numbers | DCs generated ex vivo | Posttransplant setting |
| Immature or tolerogeneic DCs | Engineered DCs | Immunomodulatory drugs | |
| Treg inhibition | |||
| Checkpoint inhibitors | |||
| Tumor defective antigen presentation and costimulation | Impaired antigen processing and presentation | T cells, NKs, and NKTs expressing CARs | Pharmacologic modulation of the epigenetic profile |
| MHC downregulation and HLA loss | Allogeneic NKs | ||
| Lack of costimulatory molecules | TCR-redirected T cells | ||
| EBV-specific T cells | |||
| Tumor resistance to cytolysis and induction of immune exhaustion | Loss of Fas/TRAIL-R | T cells, NKs, and NKTs expressing CARs | BCL-2 inhibitors |
| Release of soluble death receptors | TCR-redirected T cells | Histone deacetylase inhibitors Proteasome inhibitors | |
| Overexpression of antiapoptotic molecules | EBV-specific T cells | Checkpoint inhibitors | |
| PD-L1 expression | |||
| Tumor-associated immune-suppressive cells | Increased Tregs, TAMs, and MDSCs | DCs or engineered ex vivo expanded | Posttransplant setting |
| T cells, NKs, and NKTs expressing CARs | Lymphodepletion | ||
| Allogeneic NKs | Selective elimination or reprogramming of Tregs, TAMs, and MDSCs | ||
| TCR-redirected T cells | |||
| EBV-specific T cells | |||
| Tumor-associated soluble factors | Immunosuppressive cytokines (IL10, IL6, TGF-β, VEGF) | Additional T-cell engineering with dominant-negative receptors, chemokine receptors, favorable cytokines | Lymphodepletion |
| Chemokines (TARC) | |||
| Tumor-altered immune metabolism | Nutrient deprivation | Additional T-cell engineering to manipulate cell metabolism | Lymphodepletion |
| Hypoxia | IDO inhibitors | ||
| IDO | Adenosine receptor inhibitors |
| . | Defects . | Immune cell-based therapies . | Combinations with immune cell–based therapies . |
|---|---|---|---|
| Tumor-associated DC dysfunction | Reduced DC numbers | DCs generated ex vivo | Posttransplant setting |
| Immature or tolerogeneic DCs | Engineered DCs | Immunomodulatory drugs | |
| Treg inhibition | |||
| Checkpoint inhibitors | |||
| Tumor defective antigen presentation and costimulation | Impaired antigen processing and presentation | T cells, NKs, and NKTs expressing CARs | Pharmacologic modulation of the epigenetic profile |
| MHC downregulation and HLA loss | Allogeneic NKs | ||
| Lack of costimulatory molecules | TCR-redirected T cells | ||
| EBV-specific T cells | |||
| Tumor resistance to cytolysis and induction of immune exhaustion | Loss of Fas/TRAIL-R | T cells, NKs, and NKTs expressing CARs | BCL-2 inhibitors |
| Release of soluble death receptors | TCR-redirected T cells | Histone deacetylase inhibitors Proteasome inhibitors | |
| Overexpression of antiapoptotic molecules | EBV-specific T cells | Checkpoint inhibitors | |
| PD-L1 expression | |||
| Tumor-associated immune-suppressive cells | Increased Tregs, TAMs, and MDSCs | DCs or engineered ex vivo expanded | Posttransplant setting |
| T cells, NKs, and NKTs expressing CARs | Lymphodepletion | ||
| Allogeneic NKs | Selective elimination or reprogramming of Tregs, TAMs, and MDSCs | ||
| TCR-redirected T cells | |||
| EBV-specific T cells | |||
| Tumor-associated soluble factors | Immunosuppressive cytokines (IL10, IL6, TGF-β, VEGF) | Additional T-cell engineering with dominant-negative receptors, chemokine receptors, favorable cytokines | Lymphodepletion |
| Chemokines (TARC) | |||
| Tumor-altered immune metabolism | Nutrient deprivation | Additional T-cell engineering to manipulate cell metabolism | Lymphodepletion |
| Hypoxia | IDO inhibitors | ||
| IDO | Adenosine receptor inhibitors |