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


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.


Intratumoral cytokines Chemokines Growth factors Dendritic cells Immunosuppression 



antigen-presenting cells


dendritic cell(s)


epidermal growth factor


granulocyte-macrophage colony-stimulating factor


hepatocyte growth factor


head and neck squamous-cell carcinoma


intercellular adhesion molecule 1




interferon-gamma-inducible protein 10; CXCL10


Langerhans cells


Laser Capture Microdissection


lymph node(s)


Laser Scanning Cytometry


monocyte chemotactic protein 1; CCL2


macrophage colony-stimulating factor


macrophage inflammatory protein-3α, CCL20


natural killer


non-small cell lung cancer




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


tumor antigen(s)


tumor-associated dendritic cells


tumor-associated macrophages


transforming growth factor-β


tumor-infiltrating lymphocytes


toll-like receptor


tumor necrosis factor-α


sentinel lymph node(s)


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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