Induction of MHC antigens by tumour cell lines in response to interferons

Nouri, A. M. E.; Hussain, R.F.; Santos, Aurelio; Gillott, David J.; Oliver, R.T.D.

doi:10.1016/0959-8049(92)90467-g

Cited by 14 publications

(7 citation statements)

References 20 publications

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“…Interferon-γ has previously been shown to increase surface expression of a variety of markers (24). In the cell lines we studied we found all but a few to increase expression of MHC class I, β 2 m, and HLA-DR when cultured in the presence of interferon-γ for 72 h before analysis.…”

Section: Discussionmentioning

confidence: 56%

Defective Major Histocompatibility Complex Class I Expression in a Sarcomatoid Renal Cell Carcinoma Cell Line

Jakobsen

Restifo

Cohen

et al. 1995

Journal of Immunotherapy

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SummaryWe studied major histocompatibility complex (MHC) class I expression in 12 tumor cell culture lines established from patients with metastatic renal cell carcinoma (RCC). In one of these cell culture lines, UOK 123, we found no surface expression of β 2 -microglobulin (β 2 m) and MHC class I by flow cytometry. Immunofluorescence staining using three different monoclonal antibodies to β 2 m revealed no detectable β 2 m in the endoplasmic reticulum (ER), Golgi apparatus, cytoplasm, or on the cell surface. There was no evidence of folded class I molecules inside or on the surface of the cells; however, the ER stained intensively for unfolded class I molecules. Transient expression of β 2 m by UOK 123 after infection with a recombinant vaccinia virus containing the gene for β 2 m resulted in normal expression of both β 2 m and class I (HLA-A, B, C) determinants assessed by flow cytometry analysis. No expression of class I or β 2 m was seen with the recombinant vaccinia vector carrying a control gene. The inability of class I molecules to reach the cell surface is due to the requirement of β 2 m for proper folding and presentation of the class I MHC complex. The failure to assemble and express MHC class I complex on the cell surface renders these cells incapable of antigen presentation to cyto-toxic T cells and provides a mechanism for escape from immune recognition by the tumor.

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Section: Discussionmentioning

confidence: 56%

Defective Major Histocompatibility Complex Class I Expression in a Sarcomatoid Renal Cell Carcinoma Cell Line

Jakobsen

Restifo

Cohen

et al. 1995

Journal of Immunotherapy

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“…For example, IFN-Á-induced de novo MHC class II expression was described in normal and malignant cells such as keratinocytes, human osteogenic sarcoma, colorectal carcinoma, and melanoma cell lines (25)(26)(27). Even though the mechanism and the therapeutic value of IFN-Á treatment is not clear, immune-modulatory effects were ascribed to modifications of antigen processing and antigen presentation (28)(29)(30). Furthermore, an improved T cell-mediated killing of pancreatic carcinoma cells was described after IFN-Á stimulation (31).…”

Section: Introductionmentioning

confidence: 99%

Specific immune recognition of pancreatic carcinoma by patient-derived CD4 and CD8 T cells and its improvement by interferon-γ

Schmitz-Winnenthal

Escobedo²,

Beckhove³

et al. 2006

Int J Oncol

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Abstract. Pancreatic carcinoma is a very aggressive disease and little is known about its immunobiology. We here describe the presence in pancreatic cancer patients of spontaneously induced functional CD4 and CD8 memory/effector T cells reactive to autologous tumor cells or to the pancreatic cancer associated antigen, MUC-1. Such specific cells were present in the bone marrow or peripheral blood of most of the 23 tested patients. Low dose stimulation of primary cultures of pancreatic cancer cells with 500 IU/ml IFN-Á for 72 h enhanced HLA-I expression and induced the de novo expression of HLA-II molecules. This led to a much better immune recognition by autologous HLA-I restricted and purified CD8 T cells and allowed tumor cell recognition by HLA-II restricted purified CD4 T-helper cells. Thus, interferon-Á appears to be a useful adjuvant cytokine to enhance the immunogenicity of a patients' tumor cells and their recognition by tumor reactive immune cells.

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“…Cell lines Fen, Ha and Lan were in-house established lines from tumour biopsies of patients with transitional cell carcinoma, teratoma and seminoma respectively. For cell lines J82, Wil, RT4, Scaber, RT112, Tera I, Tera II, EP2012, 5637, SKV14 and lines see reference (Nouri et al, 1992a) The MNCs from normal individuals were separated using density gradient technique (Lymphoprep, Nycomed, Pharma), as described previously (Nouri et al, 1991). The interface cells were aspirated washed and stimulated with IL-2 (100 u ml-', Biogen) for 72-96 h (unless otherwise stated) at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Intensity of class I antigen expression on human tumour cell lines and its relevance to the efficiency of non-MHC-restricted killing

Nouri

Hussain²,

Santos³

et al. 1993

Br J Cancer

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Summary A modified tetrazolium reduction assay (MTT) was used to assess the relation between HLA class I antigen expression on tumour cells and their susceptibility as a target for non-MHC restricted LAK/NK cytotoxicity using interleukin-2 activated peripheral blood mononuclear cells (MNC) from normal individuals. At 20/1 effector/target ratio this ranged from no killing to 77%. The efficiency of killing was dependent on duration of effector cell culture with IL-2, peaking at day 10 and declining thereafter. This killing could be enhanced by addition of other cytokines including interferons alpha, beta and gamma.Study of a panel of 15 tumour cell lines using a single effector showed that there was no statistically significant inverse correlation (using Spearman rank test) between the degree of tumour class I expression and LAK/NK killing at 20/1 (r = 0.23 P = 0.39) and 10/1 (r = 0.30, P = 0.27) and at 5/1 E/T ratio r = 0.47, P = 0.08) respectively. Lack of inverse correlation between these two parameters came from study of one bladder tumour line (FEN), whose absent class I antigens had been corrected by transfection with P2 microglobulin gene. At high E/T ratio (20/1) there was an increase in the susceptibility of target cells to lysis (36% parent cell, 45% transfected cell), whilst at lower E/T ratios (1/1) there was significantly more killing of the non-transfected cells (10% vs 31%). The addition of anti-class I antibody W6/32 increased killing by 18% but this was non-specific as the same increase occurred with a class II antibody.These data suggest that overall there was not an inverse correlation between class I expression and LAK/NK killing at high E/T ratios, whilst at low (5/1 or lower) E/T ratios this correlation nearly reached statistical significance suggesting that the conflicing literature reports may be due to a threshold levels of effector cells above which the masking effects of MHC antigens disappears.

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Induction of MHC antigens by tumour cell lines in response to interferons

Cited by 14 publications

References 20 publications

Defective Major Histocompatibility Complex Class I Expression in a Sarcomatoid Renal Cell Carcinoma Cell Line

Defective Major Histocompatibility Complex Class I Expression in a Sarcomatoid Renal Cell Carcinoma Cell Line

Specific immune recognition of pancreatic carcinoma by patient-derived CD4 and CD8 T cells and its improvement by interferon-γ

Intensity of class I antigen expression on human tumour cell lines and its relevance to the efficiency of non-MHC-restricted killing

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