Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic cells: friends or enemies?

Abstract

The tumor microenvironment consists of a variable combination of tumor cells, stromal fibroblasts, endothelial cells and infiltrating leukocytes, such as macrophages, T lymphocytes, and dendritic cells. A variety of cytokines, chemokines and growth factors are produced in the local tumor environment by different cells accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of multiple cell types. The interaction between cytokines, chemokines, growth factors and their receptors forms a comprehensive network at the tumor site, which is primary responsible for overall tumor progression and spreading or induction of antitumor immune responses and tumor rejection. Although the general thought is that dendritic cells are among the first cells migrating to the tumor site and recognizing tumor cells for the induction of specific antitumor immunity, the clinical relevance of dendritic cells at the site of the tumor remains a matter of debate regarding their role in the generation of successful antitumor immune responses in human cancers. While several lines of evidence suggest that intratumoral dendritic cells play an important role in antitumor immune responses, understanding the mechanisms of dendritic cell/tumor cell interaction and modulation of activity and function of different dendritic cell subtypes at the tumor site is incomplete. This review is limited to discussing the role of intratumoral cytokine network in the understanding immunobiology of tumor-associated dendritic cells, which seems to possess different regulatory functions at the tumor site.

Inflammatory tumour cell killing by oncolytic reovirus for the treatment of melanoma

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Tumor-Derived Lactate Modifies Antitumor Immune Response: Effect on Myeloid-Derived Suppressor Cells and NK Cells

“…Developing tumors secrete a wide variety of factors including vascular endothelial growth factor, TGF-b, GM-CSF, IL-10, and PGE 2 that promote accumulation of MDSCs (13,14). MDSCs mediate immunosuppression by using two enzymes involved in arginine metabolism (ARG and NOS) and also through the enzyme IDO that is involved in tryptophan metabolism.…”

All-trans Retinoic Acid Enhances Murine Dendritic Cell Migration to Draining Lymph Nodes via the Balance of Matrix Metalloproteinases and Their Inhibitors

“…C ancers exert systemic impact on immune cell function through various mechanisms (1,2). Among these, altered dendritic cell (DC) 4 differentiation, maturation, and function are of utmost importance because DCs are the most potent APCs of the immune system.…”

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