In situ expression of B7 and CD28 receptor families in human malignant melanoma: relevance for T-cell-mediated anti-tumor immunity.
Work in animal models has suggested that interactions of members of the B7 receptor family (e.g., B7-1, B7-2) on tumor cells with their ligands CD28 and CTLA-4 on cytotoxic T cells (CTL) are important for the induction of anti-tumor immunity against malignant melanoma (MM). To determine whether these molecules are of relevance for CTL responses against human MM, we studied the expression of B7-1, B7-2, CD28 and CTLA-4 in primary tumors of MM (PMM), MM metastases (MMM) and benign melanocytic nevi (BMN) by immunohistochemistry (IH) and by reverse transcription polymerase chain reaction (RT-PCR). By RT-PCR, B7-1 and B7-2-specific mRNAs were detected in most PMM, MMM and BMN. These PCR-signals were derived from CD45(+)-infiltrating leukocytes and not from tumor cells since (I) MMM depleted of CD45+ cells contained no B7-1 or B7-2 mRNA; and (2) by IH, B7-1 and B7-2 were found on infiltrating dendritic cells, macrophages and a variable proportion of tumor-infiltrating lymphocytes (TIL) but not on melanoma cells or nevus cells. The important exceptions were 5/5 spontaneously regressing PMM, in which B7-1 and B7-2 were expressed by melanoma cells, that were surrounded by TIL expressing CD28 but not CTLA-4. We conclude that, in PMM, MMM and BMN, the majority of TIL are CD28+ and that B7-1 and B7-2 are expressed by CD45(+)-infiltrating antigen-presenting cells (APC) and TIL, but not by the tumor cells. However, in spontaneously regressing PMM, melanoma cells express B7-1, B7-2 and MHC class-I and -II antigens, particularly in areas with clinical and histological signs of an ongoing anti-tumor response. These data suggest that the absence of B7-1 and B7-2 favors the escape of MM from immunosurveillance, while B7-1, B7-2 expression enhances T-cell-mediated anti-tumor immunity.
Denfeld
R W
RW
Department of Dermatology, University of Freiburg, Germany.
Dietrich
A
A
Wuttig
C
C
Tanczos
E
E
Weiss
J M
JM
Vanscheidt
W
W
Schöpf
E
E
Simon
J C
JC
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism; D018122:B7-1 Antigen / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D018106:CD28 Antigens / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D060908:CTLA-4 Antigen; D018014:Gene Transfer Techniques; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D018796:Immunoconjugates; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008544:Melanocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D009508:Nevus, Pigmented / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D000069594:Abatacept; D017493:Leukocyte Common Antigens