Table 1.

Tumor escape and potential reversal strategies by adjuvant treatment options.

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)