TY - JOUR
T1 - Regional immunity in melanoma
T2 - Immunosuppressive changes precede nodal metastasis
AU - Mansfield, Aaron S.
AU - Holtan, Shernan G.
AU - Grotz, Travis E.
AU - Allred, Jake B.
AU - Jakub, James W.
AU - Erickson, Lori A.
AU - Markovic, Svetomir N.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
KW - angiogenesis
KW - cytotoxic T cells
KW - lymph nodes
KW - melanoma
KW - regional immunity
UR - http://www.scopus.com/inward/record.url?scp=79953303193&partnerID=8YFLogxK
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U2 - 10.1038/modpathol.2010.227
DO - 10.1038/modpathol.2010.227
M3 - Article
C2 - 21151098
AN - SCOPUS:79953303193
SN - 0893-3952
VL - 24
SP - 487
EP - 494
JO - Modern Pathology
JF - Modern Pathology
IS - 4
ER -