Understanding Dendritic Cells and Their Role in Cutaneous Carcinoma and Cancer Immunotherapy

Abstract

Dendritic cells (DC) represent a diverse group of professional antigen-presenting cells that serve to link the innate and adaptive immune systems. Their capacity to initiate a robust and antigen-specific immune response has made them the ideal candidates for cancer immunotherapies. To date, the clinical impact of DC immunotherapy has been limited, which may, in part, be explained by the complex nature of DC biology. Multiple distinct subsets of DCs have been identified in the skin, where they can be broadly subcategorized into epidermal Langerhans cells (LC), myeloid-derived dermal dendritic cells (mDC) and plasmacytoid dendritic cells (pDC). Each subset is functionally unique and may activate alternate branches of the immune system. This may be relevant for the treatment of squamous cell carcinoma, where we have shown that the tumor microenvironment may preferentially suppress the activity of mDCs, while LCs remain potent stimulators of immunity. Here, we provide an in depth analysis of DC biology, with a particular focus on skin DCs and their role in cutaneous carcinoma. We further explore the current approaches to DC immunotherapy and provide evidence for the targeting of LCs as a promising new strategy in the treatment of skin cancer.

Prognostic and predictive significance of immune cells infiltrating cutaneous melanoma

“…As the most potent antigen‐presenting cells, DCs play key roles in the immune response against tumors via processing of tumor‐associated antigens and their presentation to CD4 + and CD8 + T lymphocytes. DCs constitute a complex system of cells displaying considerable heterogeneity in phenotype, anatomical location, and functional abilities (Yanofsky et al., ). In the skin, DC types of myeloid origin include Langerhans cells and dermal DCs.…”

Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review

“…Both immunosuppression and immune T-cell polarization have demonstrated implications in carcinogenesis (8). Additionally, dendritic cell immunophenotype subsets are associated with cutaneous carcinoma prognosis (9). The complex interplay between cutaneous malignancies and the immune system offers wide therapeutic potential.…”

Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced apoptotic tumor cells on tumor cell antigens in mouse bladder cancer

“…In exploring a tumor vaccine, researchers have used a variety of strategies to develop a DC vaccine that can stimulate a tumor-specific immune response. These have mainly included DCs loaded with tumor antigens, tumor antigen sensitized DCs, and tumor antigen gene transfection DCs (Yanofsky et al, 2013). A DC vaccine with a tumor cell lysate can induce a cytotoxic T lymphocyte response, lyse tumor cells, and cause secretion of high levels of interferon-γ (Li et al, 2008).…”