Advances in dendritic cell vaccination therapy of cancer

Traditionally, vaccines have helped eradication of several infectious diseases and also saved millions of lives in the human history. Those prophylactic vaccines have acted through inducing immune responses against a live attenuated, killed organism or antigenic subunits to protect the recipient against a real infection caused by the pathogenic microorganism. Nevertheless, development of anticancer vaccines as valuable targets in human health has faced challenges and requires further optimizations. Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) that play essential roles in tumor immunotherapies through induction of CD8⁺ T cell immunity. Accordingly, various strategies have been tested to employ DCs as therapeutic vaccines for exploiting their activity against tumor cells. Application of whole tumor cells or purified/recombinant antigen peptides are the most common approaches for pulsing DCs, which then are injected back into the patients. Although some hopeful results are reported for a number of DC vaccines tested in animal and clinical trials of cancer patients, such approaches are still inefficient and require optimization. Failure of DC vaccination is postulated due to immunosuppressive tumor microenvironment (TME), overexpression of checkpoint proteins, suboptimal avidity of tumor-associated antigen (TAA)-specific T lymphocytes, and lack of appropriate adjuvants. In this review, we have an overview of the current experiments and trials evaluated the anticancer efficacy of DC vaccination as well as focusing on strategies to improve their potential including combination therapy with immune checkpoint inhibitors (ICIs).