Dendritic cells (DCs) play a critical role in orchestrating antitumor immune responses due to their capability of regulating innate and adaptive immunity. DCs can elicit tumor specific cytotoxic immunity through both the induction of antigen-specific CD4+ and CD8+ T lymphocytes and the stimulation of killing activity of innate immune cells, such as NK cells and NKT cells. Although a compelling body of preclinical studies strongly supports the potential application of DCs in the treatment of solid and hematologic tumors, DC-based immunotherapy remains rarely used in the clinical practice. Moreover, in the last decade, the clinical trials employing DC-based vaccines, often as monotherapy, showed unsatisfactory clinical benefits, hence discouraging the oncologists.

At present, the rapidly progressing advances in deciphering immunoescape mechanisms of cancer cells highlight the promising therapeutic relevance of combining classical anticancer treatments or target therapies with immunotherapeutic strategies and, in particular, with DC-based vaccines. The current challenge is the definition of the most effective and safe therapeutic combination. This may be accomplished by improving our knowledge on how conventional anticancer drugs and small molecule inhibitors could affect and modulate DC functions. Moreover, a deeper knowledge of molecular mechanisms, signaling pathways and epigenetic regulation of DC biology is needed to exploit the full potential of DC-based immunotherapies. An emerging area of clinical relevance is the combination of DC-based vaccines with immune checkpoint inhibition, whose rationale is supported by convincing preclinical data demonstrating therapeutic synergism and improved efficacy with a retained safety profile.

On this ground, this Research Topic aims to provide a comprehensive overview of the recent advances in developing optimized DC-based cancer vaccines and their experimental and clinical exploitation in combination with different therapies. To this end, we would encourage submission of Original Research articles, Reviews, Mini-Reviews and Opinion articles that cover, but are not limited to, the following topics:

· Modulation of DC functions by anticancer treatments
· Role of different signaling pathways in DC maturation and activation in cancer
· Metabolic control of DC function in cancer
· Epigenetic mechanisms underlying DC function regulation in cancer
· Role of DC in the induction of T cell response vs T cell tolerance in cancer
· Cross-talk between DC and other immune effectors in anticancer immunity
· Potential predictive markers of a successful response to DC-based therapeutic approaches
· Novel technology development to target and activate anticancer DC in vivo

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Frontiers in Immunology

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