The frequency of major histocompatibility complex antigen abnormalities in urological tumours and their correction by gene transfection or cytokine stimulation.
There is increasing evidence that loss of major histocompatibility complex (MHC) antigens from tumors may be a factor in escape from immune surveillance. In an attempt to quantify this phenomenon in bladder tumors, frozen sections were stained immunochemically and cell lines were tested in a radiobinding assay before and after treatment with interferon gamma (IFN gamma) and after attempts to correct the defect by normal human leukocyte antigen (HLA) gene transfection. Study of 68 tumor sections with W6/32 antibody against monomorphic class I demonstrated that 42% had reduced or absent staining compared with the intensity of stromal staining. Ten percent of cases had complete absence with W6/32, all of which were also negative for beta 2-microglobulin (beta 2-m) expression. Use of polymorphic antibodies for A2, A3, Bw4, and Bw6 increased this frequency of defects to 73%. Study of 21 tumor cell lines with W6/32 demonstrated negative staining in five (23%) that could not be induced by IFN gamma and reduced staining in three (14%) that could be increased by IFN gamma, the remainder showing normal levels unaffected by IFN gamma. An additional six (28%) failed to express class II in response to IFN gamma, leading to an overall incidence of abnormality of 65%. In no case did cotransfection of one cell line with a defect in one case transfection of beta 2-m gene into a class I negative line of fully assembled MHC class I antigens. It is concluded that the majority of tumor cells demonstrate some form of MHC class I and II defects.(ABSTRACT TRUNCATED AT 250 WORDS)
Nouri
A M
AM
Royal London Hospital, England.
Hussain
R F
RF
Oliver
R T
RT
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001613:beta 2-Microglobulin / Q000172:deficiency
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D016898:Interferon-alpha; D001613:beta 2-Microglobulin; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma