Regional immunity in melanoma

Immunosuppressive changes precede nodal metastasis

Aaron Mansfield, Shernan G. Holtan, Travis E. Grotz, Jake B. Allred, James W Jakub, Lori A. Erickson, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

In order to characterize the degree of immunosuppression in regional immunity in patients with melanoma, we used immunohistochemistry to analyze markers of T-cell subtype and polarity, costimulation, dendritic cell maturation, monocytes, lymphatic vasculature, and angiogenesis. Specifically, we analyzed expression of CD4, CD8, CD14, CD40, CD86, CD123, HLA-DR, IL-10, LYVE, VEGFR3, and VEGF-C in lymph nodes. We compared sentinel lymph nodes with and without metastasis from patients with melanoma with both infection inflamed (reactive) and dormant human lymph nodes. There were no differences demonstrated between sentinel lymph nodes with or without metastasis from patients with melanoma in any of the markers that were tested. Both groups of sentinel lymph nodes had fewer CD8 T cells than either set of control nodes. Whereas the infection inflamed lymph nodes demonstrated Th2 polarity, the dormant lymph nodes demonstrated Th1 polarity. In conclusion, changes in regional immunity appeared to precede metastasis in melanoma. Whether there was tumor present in sentinel lymph nodes or not, these nodes demonstrated a marked decrease in cytotoxic T cells compared with both sets of controls. Furthermore, the control lymph nodes used for comparison can significantly impact interpretation, as the dormant and reactive lymph nodes markedly varied in their immune profiles. These immunologic changes may explain the successful metastasis of melanoma in the midst of the immune environment of the sentinel lymph node, and lend insights into the mechanisms of lymphatic metastases in other solid malignancies.

Original languageEnglish (US)
Pages (from-to)487-494
Number of pages8
JournalModern Pathology
Volume24
Issue number4
DOIs
StatePublished - Apr 2011

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Immunosuppressive Agents
Immunity
Melanoma
Lymph Nodes
Neoplasm Metastasis
T-Lymphocytes
Vascular Endothelial Growth Factor C
Lymphatic Metastasis
Cell Polarity
HLA-DR Antigens
Infection
Interleukin-10
Immunosuppression
Dendritic Cells
Monocytes
Neoplasms
Immunohistochemistry
Sentinel Lymph Node

Keywords

  • angiogenesis
  • cytotoxic T cells
  • lymph nodes
  • melanoma
  • regional immunity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Regional immunity in melanoma : Immunosuppressive changes precede nodal metastasis. / Mansfield, Aaron; Holtan, Shernan G.; Grotz, Travis E.; Allred, Jake B.; Jakub, James W; Erickson, Lori A.; Markovic, Svetomir Nenad.

In: Modern Pathology, Vol. 24, No. 4, 04.2011, p. 487-494.

Research output: Contribution to journalArticle

Mansfield, Aaron ; Holtan, Shernan G. ; Grotz, Travis E. ; Allred, Jake B. ; Jakub, James W ; Erickson, Lori A. ; Markovic, Svetomir Nenad. / Regional immunity in melanoma : Immunosuppressive changes precede nodal metastasis. In: Modern Pathology. 2011 ; Vol. 24, No. 4. pp. 487-494.
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