Molecular mechanisms involved in dendritic cell dysfunction in cancer.

ABSTRACT

Dendritic cells (DC) play a pivotal role in the tumor microenvironment (TME). As the primary antigen-presenting cells in the tumor, DCs modulate anti-tumor responses by regulating the magnitude and duration of infiltrating cytotoxic T lymphocyte responses. Unfortunately, due to the immunosuppressive nature of the TME, as well as the inherent plasticity of DCs, tumor DCs are often dysfunctional, a phenomenon that contributes to immune evasion. Recent progresses in our understanding of tumor DC biology have revealed potential molecular targets that allow us to improve tumor DC immunogenicity and cancer immunotherapy. Here, we review the molecular mechanisms that drive tumor DC dysfunction. We discuss recent advances in our understanding of tumor DC ontogeny, tumor DC subset heterogeneity, and factors in the tumor microenvironment that affect DC recruitment, differentiation, and function. Finally, we describe potential strategies to optimize tumor DC function in the context of cancer therapy.