Enhanced expression of interferon-gamma-induced antigen-processing machinery components in a spontaneously occurring cancer.
In human tumors, changes in the surface expression and/or function of major histocompatibility complex (MHC) class I antigens are frequently found and may provide malignant cells with a mechanism to escape control of the immune system. This altered human lymphocyte antigen (HLA) class I phenotype can be caused by either structural alterations or dysregulation of genes encoding subunits of HLA class I antigens and/or components of the MHC class I antigen-processing machinery (APM). Herein we analyze the expression of several proteins involved in the generation of MHC class I epitopes in feline injection site sarcoma, a spontaneously occurring tumor in cats that is an informative model for the study of tumor biology in other species, including humans. Eighteen surgically removed primary fibrosarcoma lesions were analyzed, and an enhanced expression of two catalytic subunits of immunoproteasomes, PA28 and leucine aminopeptidase, was found in tumors compared to matched normal tissues. As a functional counterpart of these changes in protein levels, proteasomal activities were increased in tissue extracts from fibrosarcomas. Taken together, these results suggest that alterations in the APM system may account for reduced processing of selected tumor antigens and may potentially provide neoplastic fibroblasts with a mechanism for escape from T-cell recognition and destruction.
Cerruti
Fulvia
F
Department of Veterinary Morphophysiology, University of Turin, Grugliasco, TO, Italy.
Martano
Marina
M
Petterino
Claudio
C
Bollo
Enrico
E
Morello
Emanuela
E
Bruno
Renato
R
Buracco
Paolo
P
Cascio
Paolo
P
D000818:Animals; D017951:Antigen Presentation; D002371:Cat Diseases / Q000276:immunology*; D002415:Cats; D003546:Cysteine Endopeptidases / Q000032:analysis; D005260:Female; D005354:Fibrosarcoma / Q000201:enzymology / Q000276:immunology* / Q000662:veterinary; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D007931:Leucyl Aminopeptidase / Q000032:analysis; D008297:Male; D009097:Multienzyme Complexes / Q000032:analysis; D046988:Proteasome Endopeptidase Complex; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019139:Tumor Escape
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; C071313:LMP-2 protein; D007371:Interferon-gamma; D007931:Leucyl Aminopeptidase; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex