Immunotherapy of HPV-associated head and neck cancer: Critical parameters

Abstract

Various arguments support the development of a vaccine targeting human papillomavirus (HPV) for the treatment of HPV-associated head and neck cancer. However, the mucosal localization of this tumor, the HPV-driven downregulation of MHC Class I molecules and various other immunosuppressive mechanisms must be carefully considered to improve the clinical efficacy of such an immunotherapeutic strategy.

Keywords: HPV; PD1; head and neck; immunotherapy; mucosal immunity.

Figure 1. Critical parameters to improve the efficacy of therapeutic HPV-targeting vaccines in head and neck cancer patients. (A) The intranasal (mucosal) route of immunization significantly potentiates the efficacy of HPV-targeting vaccines. (B) As HPV proteins including E5 and E7 can downregulate MHC Class I molecules, measuring the expression of the latter on the surface of tumor cells may allow for the selection of patients who are most likely to respond to anticancer immune responses elicited by HPV-targeting vaccines. (C) Malignant cells activate various immunosuppressive mechanisms, including the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressive cells, the activation of immune checkpoints on activated T cells, etc. Hence, drugs that alleviate immunosuppression should be combined with anticancer vaccines to improve their therapeutic potential.