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

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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.

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Abbreviations

APC:

antigen-presenting cells

DC:

dendritic cell(s)

EGF:

epidermal growth factor

GM-CSF:

granulocyte-macrophage colony-stimulating factor

HGF:

hepatocyte growth factor

HNSCC:

head and neck squamous-cell carcinoma

ICAM-1:

intercellular adhesion molecule 1

IDO:

indoleamine-2,3-deoxygenase

IP-10:

interferon-gamma-inducible protein 10; CXCL10

LC:

Langerhans cells

LCM:

Laser Capture Microdissection

LN:

lymph node(s)

LSC:

Laser Scanning Cytometry

MCP-1:

monocyte chemotactic protein 1; CCL2

M-CSF:

macrophage colony-stimulating factor

MIP-3α:

macrophage inflammatory protein-3α, CCL20

NK:

natural killer

NSCLC:

non-small cell lung cancer

PHA:

phytohemagglutinin

RANTES:

regulated upon activation, normal T cell expressed and secreted chemokine; CCL5

TA:

tumor antigen(s)

TADC:

tumor-associated dendritic cells

TAM:

tumor-associated macrophages

TGF-β:

transforming growth factor-β

TIL:

tumor-infiltrating lymphocytes

TLR:

toll-like receptor

TNF-α:

tumor necrosis factor-α

SLN:

sentinel lymph node(s)

VEGF:

vascular endothelial growth factor

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Shurin, M.R., Shurin, G.V., Lokshin, A. et al. Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic cells: friends or enemies?. Cancer Metastasis Rev 25, 333–356 (2006). https://doi.org/10.1007/s10555-006-9010-6

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