Vaccines as Priming Tools for T Cell Therapy for Epithelial Cancers

SIMPLE SUMMARY: Despite all of the impressive progress that has been made in the field of cancer therapy, cancer continues to devastate the lives of many. Recent efforts have focused on taking advantage of the patients’ immune system, modifying and employing it to attack cancer cells more efficiently. Therapeutic cancer vaccines are part of the armamentarium used for that purpose. In this review, we discuss the role of the immune system in the fight against cancer, the various strategies that are aimed at engaging the immune system, and how therapeutic cancer vaccines can be used as a self-standing strategy or as a means to leverage other immunotherapies to deliver more efficient results. We elaborate on the obstacles that are present, why immune therapies do not work equally well on all patients, and how vaccines can potentially play a role in improving cancer outcomes. ABSTRACT: Impressive progress has recently been made in the field of cancer immunotherapy with the adoptive transfer of T cells, a successful personalized strategy, and checkpoint inhibitors (CPI) having extended the survival of numerous patients. However, not all patients have been able to benefit from these innovations. A key determinant of the responsiveness to cancer immunotherapies is the presence of T cells within the tumors. These tumor-infiltrating lymphocytes (TILs) are crucial in controlling tumor growth and their activity is being potentiated by immunotherapies. Although some epithelial cancers are associated with spontaneous T-cell and B-cell responses, which makes them good candidates for immunotherapies, it remains to create strategies that would promote lymphocyte infiltration and enable sustained immune responses in immune-resistant tumors. Therapeutic cancer vaccines hold the potential of being able to render “cold”, poorly infiltrated tumors into “hot” tumors that would be receptive to cellular immunotherapies. In this review, we elaborate on the obstacles that need to be overcome and the strategies that are being explored to that end, including various types of antigen repertoires and different vaccine platforms and combinations with other available treatments.