Dendritic Cells in the Cancer Microenvironment

Abstract

The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs) represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

“…Among the many components of this tumor microenvironment is a population of regDCs, which exert profound immune suppressive effects on T cells and, probably, other immune effector cells, and interact with different myeloid and lymphoid regulatory cells. Recently, different kinds of regulatory or tolerogenic DCs have been reported [1,102]. Regulatory DCs can suppress T cell activation and proliferation via inducing Treg cell expansion or generation, or T cell anergy.…”

Improvement of DC vaccine with ALA-PDT induced immunogenic apoptotic cells for skin squamous cell carcinoma

“…In the immune system, dendritic cells (DCs) are the most important antigen-presenting cells (APCs) [4][5][6][7]. They are crucial in antigen updating, processing, and presentation to T cells, to induce tumor-specific immune responses [8][9]. Recent studies show that DC-based vaccines obtained through stimulation of DCs by ex vivo prepared tumor antigens have yielded promising results in the treatment of cervical cancer, melanoma, and ovarian cancer [10][11].…”

Gangliosides and Antigangliosides in Malignant Melanoma

“…Monosialogangliosides suppress cell growth (GM1-MMP9, GM1-PDGF, GM1-NGF, GM3-EGF, GM3-IGFs, GM2-pFAK), while polisialogangliosides stimulate cell growth (GD3 binding integrin, p-FAK, pp130Cas, p=paxilin, p-Yes or GD2 binding p-FAK, p-p38, c-Met) [65]. The transduction mechanism is complex including complex signaling pathways (p38-MAPK, Erk1/2, p13k/AKT, JNK1/2/3) [65][66][67][68][69][70]. Gangliosides act as inhibitors or promoters of cell apoptosis in melanoma [71,72].…”