Effect of gamma interferon on HLA class‐I and ‐II transcription and protein expression in human breast adenocarcinoma cell lines

Jabrane‐Ferrat, Nabila; Faille, A; Loiseau, Pascale; Poirier, Odette; Charron, Dominique; Calvo, Fabien

doi:10.1002/ijc.2910450630

Cited by 30 publications

(20 citation statements)

References 41 publications

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“…For example, E 2 treatment attenuated HLA-DR in MCF-7 and BT-474, but not in T47D. This finding is compatible with an older study in which BCCL, cultured in E 2 -sufficient medium, exhibited a hierarchy of IFN-γ inducible HLA-DR levels with T47D>MCF-7>BT-474 [6]. Differential HLA-II in these cells is not surprising, given that ER + BCCL, although expressing many of the same genes associated with a luminal subtype, will differ in expression of many other genes [53], which may or may not be regulated by E 2 .…”

Section: Discussionsupporting

confidence: 88%

“…Typically, HLA-II expression is limited to professional antigen presenting cells (pAPC), but is induced by IFN-γ on most cell types including those derived from cancer [5], [6]. HLA-DR positive tumor cells have been described in several malignancies, such as melanoma [7], colon [8], [9] and breast [10]–[12], but the underlying mechanisms are likely diverse.…”

Section: Introductionmentioning

confidence: 99%

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Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

et al. 2014

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The coordinate regulation of HLA class II (HLA-II) is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER) and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E2) and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER− and ER+ breast cancer cell lines, we showed that E2 attenuated HLA-DR in two ER+ lines (MCF-7 and BT-474), but not in T47D, while it augmented expression in ER− lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s), we used paired transfectants: ERα+ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene) and ERα− VC5 (MDA-MB-231 c10A transfected with the empty vector), treated or not with E2 and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E2 treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E2 in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα− breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα+ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

et al. 2014

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“…Unlike HLA class I, HLA class II molecules are not normally present on resting epithelial cells, although they are detected de novo in the lactating breast and in a subset of breast carcinomas. 6 They can also be induced in vitro on many cell types, including breast cancer cell lines, by interferon-␥ (IFN-␥) 7,8 and other immunomodulators, 9,10 suggesting that in situ expression on carcinoma cells may be regulated by cytokines and/or hormones. Antigen presentation by HLA class II ϩ breast cancer cells, which lack costimulatory molecules typically found on professional antigen presenting cells (APCs), could potentially induce T-cell anergy.…”

mentioning

confidence: 99%

HLA‐DRB alleles are differentially expressed by tumor cells in breast carcinoma

Oldford

Robb

Watson

et al. 2004

Intl Journal of Cancer

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The biologic and prognostic significance of HLA-DR expression and T-cell infiltration in breast carcinoma are presently controversial. To test the hypothesis that these factors are influenced by particular HLA-DRB alleles, 52 breast tumor samples, composed of 26 DRB1*04 and 26 non-DRB1*04 tumors, were assessed using immunohistochemistry for expression of DR and its associated invariant chain (Ii) and for infiltrating CD3 ؉ T cells. While DR expression by tumor cells was significantly associated with T-cell infiltration, DRB1*04 tumors were more frequently DR ؉ Ii ؉ and contained smaller CD3 ؉ infiltrates than non-DRB1*04 tumors. This difference was largely attributable to DRB1*07 tumors, which were typically DR ؊ Ii ؊ , although they contained similar numbers of T cells to DR ؉ Ii ؉ tumors. Further analysis of DR ؉ tumors using allotype discriminating antibodies revealed that DRB1*04 alleles were always expressed, while non-DRB1*04 alleles were inconsistently expressed. The results of this study provide the first reported evidence that DRB alleles influence DR expression and T-cell infiltration in breast carcinoma and suggest that multiple factors contribute to DR expression. Ongoing studies aimed at elucidating the molecular and immunologic mechanisms controlling differential DR expression and implications for prognosis and outcome should further our understanding of the antitumor immune response and evasion strategies employed by tumor cells. © 2004 Wiley-Liss, Inc. Key words: HLA-DR expression; HLA-DRB alleles; T-cell infiltration; breast carcinoma; invariant chainA prerequisite for tumor eradication by CD8 ϩ cytolytic T cells is recognition of tumor antigen presented by HLA class I molecules on the tumor cells and this is reflected by the numerous studies showing loss or downregulation of HLA class I on established tumors. 1,2 Optimal antitumor immunity also requires participation of CD4 ϩ T cells, which recognize tumor peptides presented by HLA class II molecules (HLA-DR, -DP, -DQ). [3][4][5] However, the importance of HLA class II expression on breast carcinoma cells and implications for antitumor immunity are currently unclear. Unlike HLA class I, HLA class II molecules are not normally present on resting epithelial cells, although they are detected de novo in the lactating breast and in a subset of breast carcinomas. 6 They can also be induced in vitro on many cell types, including breast cancer cell lines, by interferon-␥ (IFN-␥) 7,8 and other immunomodulators, 9,10 suggesting that in situ expression on carcinoma cells may be regulated by cytokines and/or hormones. Antigen presentation by HLA class II ϩ breast cancer cells, which lack costimulatory molecules typically found on professional antigen presenting cells (APCs), could potentially induce T-cell anergy. However, reports of direct recognition of tumor cells by HLA class II-restricted CD4 ϩ T cells 11,12 suggest that HLA class II ϩ tumor cells play an important role in determining the outcome of an antitumor immune response.Studies investigating e...

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“…However, it is generally assumed that the mechanism by which HLA class II antigens are up-regulated on breast carcinoma cells is via the IFN-y inducible pathway, since constitutive HLA class II antigen expression is associated with constitutive CIITA transcription in melanoma cells [138]. Indeed IFN-, can induce HLA class II antigen expression on many cell types including breast carcinoma cell lines [59,128,131,132,[139][140][141][142][143]. However, to the best our knowledge the frequency of CIITA expression in breast carcinoma lesions has yet to be investigated.…”

Section: Cytokine And/or Hormonal Modulationmentioning

confidence: 99%

CTL-Tumor Cell Interaction: The Generation of Molecular Probes of Monitoring the HLA-A*0201-HER-2/neu Peptide Complex

Campoli¹

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and ABSTRACT (Maximum 200 Words)The overall goal of this project is to probe the CTL -tumor cell interaction by generating scFv probes that are able to recognize the HLA-A*0201-HER-2/neu 3 69_ 377 peptide complex. In the 12 month period covered by this report, I have successfully generated HLA-A*0201-HER-2/neu 3 69_ 377 complexes, and have isolated two scFv fragment clones that recognize this complex. In addition, I have started to analyze the expression levels of antigen processing machinery (APM) components, HLA class I antigens and P2m in several breast carcinoma cell lines. This analysis takes advantage of the availability of a wide panel of mAb to these antigens that several investigators in our laboratory, including myself, have developed and characterized. Collectively, the results we have obtained strongly support our future analysis to correlate the expression levels of APM components, HLA class I antigens, 32m and HER-2/neu with the levels of HLA-A*0201-HER-2/neu 3 69_ 37 7 complexes on breast carcinoma cells and lesions. The information derived from these studies is expected to contribute to our knowledge of the variables that influence the levels of HLA class I antigen-TAA derived peptide complex expression on breast carcinoma cells. I have successfully initiated many of the project tasks outlined in the Statement of Work. In collaboration with other investigators from our laboratory, I participated in the development and characterization of a panel of monoclonal antibodies (mAb) that are specific for proteasome and immunoproteasome subunits. The availability of these mAb, along with panels of mAb that recognize other antigen processing machinery (APM) components as well as surface HLA class I antigen and 032-microglobulin (032m), have enabled me to analyze the expression of these antigens in several breast carcinoma cell lines. In addition, I have been able to generate and purify HLA-A*0201-HER-2/neu 369 . 377 peptide complexes. By panning a semi-synthetic phage display scFv library with these complexes, I have successfully isolated two scFv fragment clones that react specifically with this complex.An immediate future goal of this project will be to increase the avidity of the HLA-A*0201-HER-2/neu 369 . 377 peptide complex-specific scFv fragments by generating scFv tetramers. In addition, the expression levels of APM components, HLA class I antigen and 032m on other breast carcinoma cell lines and on frozen section...

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Effect of gamma interferon on HLA class‐I and ‐II transcription and protein expression in human breast adenocarcinoma cell lines

Cited by 30 publications

References 41 publications

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

HLA‐DRB alleles are differentially expressed by tumor cells in breast carcinoma

CTL-Tumor Cell Interaction: The Generation of Molecular Probes of Monitoring the HLA-A*0201-HER-2/neu Peptide Complex

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