Table 1.
Tumor evasion mechanism | Desired effect | Potential reversal strategy |
---|---|---|
Loss of intracellular proteasomal antigen processing, transport (TAP deletion) and MHC-loading (beta2-microglobulin deletion) | Restoration of antigen-processing and MHC-loading, for sufficient tumor-antigen presentation | Interferon-γ treatment of the tumor |
Silencing of MHC genes | Restoration of MHC-expression | Interferon-γ treatment, application of hypomethylating agents |
Loss of T cell costimulation (e.g., CD80/86, and CD54, CD58) | Restoration of costimulatory molecules | Toll-like receptor stimulation, interferon treatment |
Unfavourable microenvironment for CTL-response | proinflammatory microenvironment for CTL-response | Application of immune response modifiers, suitable vaccine adjuvants, and induction of CD4 T helper cells |
| ||
Role of T cells | ||
| ||
Too few tumor-specific T cells | Induction of more CTL with lytic activity, broader T cell response including CD4 T-helper cells | Specific CTL stimulation and expansion. Vaccination with single or multiepitope vaccines including MHC class I and II peptides. Induction and expansion of CD4 T-helper cells. |
Loss of immunodominant tumor antigen | Direction of the immune response to other antigens or epitopes | Identification of optimal MHC-class I and II epitopes. Reexpression of the tumor-antigen |
Suppressive Treg effects | Inhibition of deleterious T-cell effects | Modulation/reduction of Treg by pretherapeutic treatment with antibodies or preferentially Treg targeting chemotherapeutic agents |
Tumor-induced T cell apoptosis | Rescue of apoptotic T cells | T cell protection by: (i) reversal of redox potential (ii) treatment with anti-apoptotic drugs (iii) blocking of proapoptotic molecules (e.g., CD95) |