Type I interferon-associated recruitment of cytotoxic lymphocytes: a common mechanism in regressive melanocytic lesions.
We studied 253 primary melanomas of the skin for histologic signs of regression. Detailed immunohistologic analyses, including expression of MxA (an antiviral protein specifically induced by type I interferons), the chemokine IP10/CXCL10, the chemokine receptor CXCR3, and the cytotoxic molecule granzyme B, were performed for 14 typical regressive tumors and 20 control samples (congenital nevi, halo nevi, unaffected skin). We found high expression of MxA, indicating local type I interferon production, in inflamed regressive melanocytic lesions, along with large numbers of natural interferon-producing plasmacytoid dendritic cells, CXCR3+ lymphocytes, and granzyme B+ lymphocytes. We also detected high expression of the interferon-induced chemokine IP10/CXCL10, linking type I interferon production and recruitment of CXCR3+ lymphocytes. Our results provide evidence that endogenous activation of type I interferons, infiltration of plasmacytoid dendritic cells, and recruitment of CXCR3+ and granzyme B+ lymphocytes are involved in spontaneous regression of melanoma and other melanocytic lesions. We believe this cytotoxic immune response represents an evolutionarily conserved pathway against intracellular pathogens.
Wenzel
Joerg
J
Department of Dermatology, University of Bonn, Bonn, Germany.
Bekisch
Barbara
B
Uerlich
Manfred
M
Haller
Otto
O
Bieber
Thomas
T
Tüting
Thomas
T
D002465:Cell Movement / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D064547:Myxovirus Resistance Proteins; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*
C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; C088546:GZMK protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D019204:GTP-Binding Proteins