Synergistic potential of immune checkpoint inhibitors and therapeutic cancer vaccines

Cancer vaccines and immune checkpoint inhibitors (ICIs) function at different stages of the cancer immune cycle due to their distinct mechanisms of action. Therapeutic cancer vaccines enhance the activation and infiltration of cytotoxic immune cells into the tumor microenvironment (TME), while ICIs, prevent and/or reverse the dysfunction of these immune cells. The efficacy of both classes of immunotherapy has been evaluated in mon-otherapy, but they have been met with several challenges. Although therapeutic cancer vaccines can activate anti-tumor immune responses, these responses are susceptible to attenuation by immunoregulatory molecules. Similarly, ICIs are ineffective in the absence of tumor-infiltrating lymphocytes (TILs). Further, ICIs are often associated with immune-related adverse effects that may limit quality of life and compliance. However, the combination of the improved immunogenicity afforded by cancer vaccines and restrained immunosuppression provided by immune checkpoint inhibitors may provide a suitable platform for therapeutic synergism. In this review, we revisit the history and various classifications of therapeutic cancer vaccines. We also provide a summary of the currently approved ICIs. Finally, we provide mechanistic insights into the synergism between ICIs and cancer vaccines.