title: HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas.
abstract: Primary cutaneous lymphomas (CLs) constitute a spectrum of diseases characterized by a clonal accumulation of lymphocytes in the skin. Most CLs display a T(h)2 cytokine profile, including expression of interleukin-10 (IL-10). Because the up-regulation of HLA-G, a nonclassical class Ib molecule inducible by IL-10, might account for the immunescape of the malignant clone, HLA-G and IL-10 expression has been investigated in 45 cases of primary CL (10 of B-cell and 35 of T-cell origin) with quantitative polymerase chain reaction (PCR) and immunohistochemistry. HLA-G message was present in all cutaneous B-cell (CBCL) and T-cell (CTCL) lymphomas evaluated. Immunohistochemistry revealed HLA-G protein expression in 23 (51%) of 45 cases (7 of 10 CBCL, 16 of 35 CTCL). While in CBCL mostly indolent types displayed HLA-G positivity, in CTCL HLA-G expression was associated with high-grade histology and advanced stage of the disease. Except for neoplastic and infiltrating lymphocytes, other cells such as macrophages and dendritic cells showed HLA-G immunoreactivity. Furthermore, IL-10 protein expression was demonstrated in 16 (73%) of 22 HLA-G(+) cases, which correlated with HLA-G protein presence (P <.001). HLA-G up-regulation together with IL-10 expression in CL might additionally contribute to the evasion of immunosurveillance and facilitate the transition from low- to high-grade lymphomas.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Urosevic
authors.forename: Joerg
authors.initials: J
authors.lastname: Willers
authors.forename: Beatrix
authors.initials: B
authors.lastname: Mueller
authors.forename: Werner
authors.initials: W
authors.lastname: Kempf
authors.forename: Guenter
authors.initials: G
authors.lastname: Burg
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003199:Computer Systems; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007157:Immunologic Surveillance; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016753:Interleukin-10