T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

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)