Dendritic Cell Cancer Vaccines: A Focused Review.

Dendritic cells (DCs) are the most potent professional antigen-presenting cells to activate both CD4+ and CD8+ T lymphocytes. When immature, they take up and process antigens efficiently. When mature, they express high levels of MHC class I and II molecules and costimulatory molecules on their surface and secrete both IL-12 and IL-15 that can activate and steer T cells. However, in patients with cancer or tumor-bearing animals, cancers secrete cytokines that suppress DC development or maturation. To circumvent this barrier to immunization against cancer, strategies have been developed to grow and mature DCs ex vivo from precursors, such as peripheral blood monocytes or bone marrow precursors, induce expression of tumor antigens ex vivo, and then administer the autologous DCs to the patient as a vaccine. The DCs may be coated with synthetic antigenic peptides or transduced with a virus expressing the tumor antigen (see Note 1). Both of these have been used in early clinical trials with promising immunogenicity. Such cancer vaccines may be especially critical for "cold" tumors that do not induce a sufficient immune response by themselves to be amenable to checkpoint inhibitor therapy or blockade of other negative regulators of immunity but with a cancer vaccine to induce the immune response, may become responsive to such immunotherapies. Conversely, cancer vaccines should become more effective if immunosuppressive mechanisms are blocked. Thus, the two approaches should synergize to optimize anticancer immune responses and reject the cancer like an allogeneic organ transplant.