New approaches in vaccine-based immunotherapy for human papillomavirus-induced cancer

• Combination treatment must increase the level of intra-tumoral cytotoxic T cells.
• Conventional treatment synergizes with therapeutic cancer vaccination.
• Understanding of escape from immunotherapy allows targeting of the mechanism(s).

The identification of human papillomavirus as the etiological factor for cervical cancer provides an opportunity to treat these malignancies by vaccination. Although therapeutic vaccination against viral oncogenes regularly induces a specific T cell response, clinical effectivity remains low. Three factors are particularly important for clinical outcome: the balance between cytotoxic T cells and regulatory immune subsets, the balance between cytotoxic T cells and tumor cells and finally the killing efficiency of cytotoxic T cells within the tumor. To improve these three factors, therapeutic vaccination is combined with other treatments. Here, we review those studies that are based on understanding the inhibitory mechanisms that prevent unleashing the full power of therapeutic vaccine-induced T cells and utilize combinatorial interventions based on these insights.