Cancer and Metastasis Reviews

, 25:333 | Cite as

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

  • Michael R. Shurin
  • Galina V. Shurin
  • Anna Lokshin
  • Zoya R. Yurkovetsky
  • Dmitry W. Gutkin
  • Gurkamal Chatta
  • Hua Zhong
  • Baohui Han
  • Robert L. Ferris
Article

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.

Keywords

Intratumoral cytokines Chemokines Growth factors Dendritic cells Immunosuppression 

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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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Michael R. Shurin
    • 1
    • 2
    • 7
  • Galina V. Shurin
    • 1
  • Anna Lokshin
    • 3
  • Zoya R. Yurkovetsky
    • 3
  • Dmitry W. Gutkin
    • 5
  • Gurkamal Chatta
    • 3
  • Hua Zhong
    • 6
  • Baohui Han
    • 6
  • Robert L. Ferris
    • 2
    • 4
  1. 1.Department of PathologyUniversity of Pittsburgh Medical Center and Cancer InstitutePittsburghUSA
  2. 2.Department of ImmunologyUniversity of Pittsburgh Medical Center and Cancer InstitutePittsburghUSA
  3. 3.Department of MedicineUniversity of Pittsburgh Medical Center and Cancer InstitutePittsburghUSA
  4. 4.Department of OtolaryngologyUniversity of Pittsburgh Medical Center and Cancer InstitutePittsburghUSA
  5. 5.VA Pittsburgh Healthcare SystemPittsburghUSA
  6. 6.Shanghai Chest HospitalShanghaiChina
  7. 7.Clinical ImmunopathologyPittsburghUSA

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