Different Patterns of Hla‐dr Antigen Expression in Normal Epithelium, Hyperplastic and Neoplastic Malignant Lesions of the Breast

Concha, Ángel; Ruiz‐Cabello, Francisco; Cabrera, Teresa; Nogales, F.; Collado, Antonia; Garrido, Federico

doi:10.1111/j.1744-313x.1995.tb00246.x

Cited by 33 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many studies have showed that MHC-class II antigens play a role in progression of malignant tumors via immunologic modification. [26][27][28][29][30][31] Our current results were consistent with their results. In this regard, our finding is not a new one.…”

Section: Discussionsupporting

confidence: 83%

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

Matoba

Iizuka

Gondo

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of the high frequency of intrahepatic recurrence (IHR), particularly early IHR within 1 year of hepatectomy. To search for genes involved in early IHR, we performed DNA microarray analysis in a training set of 33 HCCs and selected 46 genes linked to early IHR from approximately 6,000 genes by means of a supervised learning method. Gene selection was validated by a false discovery rate of 0.37%. The 46 genes included many immune response-related genes, which were all downregulated in HCCs with early IHR. Four of these genes (HLA-DRA, HLA-DRB1, HLA-DG and HLA-DQA), encoding MHC class II antigens, were coordinately downregulated in HCCs with early IHR compared to levels in HCCs with nonrecurrence. A cluster analysis reproduced expression patterns of the 4 MHC class II genes in 27 blinded HCC samples. To localize the major site of production of HLA-DR protein in the tumor, we used 50 frozen specimens from 50 HCCs. Immunofluorescence staining showed that HLA-DR protein levels in tumor cells, but not in stromal cells, were associated with the transcription levels of HLA-DRA determined by both DNA microarray analysis and real-time quantitative reverse transcription-PCR. Univariate analysis showed that tumor HLA-DR protein expression, pTNM stage and venous invasion were associated with early IHR. Multivariate analysis showed that tumor HLA-DR protein expression was one of the independent risk factors for early IHR, suggesting HLA-DR protein potential as a biomarker and a molecular target for therapeutic intervention. ' 2005 Wiley-Liss, Inc.

show abstract

Section: Discussionsupporting

confidence: 83%

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

Matoba

Iizuka

Gondo

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…12 The frequency of these changes varies among the different types of hematopoietic and solid tumors depending on their origin and/or molecular phenotype 23,30,31 : for example, more than 80% of ductal breast carcinoma lesions analyzed lack HLA class II antigen expression. 29,30 In contrast, about 50% of papillary thyroid carcinoma and 60% of primary melanoma express HLA class II antigens 31,32 suggesting a gain of HLA class II antigen expression in these tumor types. In addition, a heterogeneous intra-tumoral HLA class II antigen expression pattern was detected in HLA class II antigen-positive tumor lesions.…”

Section: Expression Of Hla Class II Antigens In Malignant Tumorsmentioning

confidence: 99%

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

View full text Add to dashboard Cite

The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4 C T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4 C T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease. Many types of human cancers express HLA class II antigens, although with marked differences in their frequency. Some types of cancer lack HLA class II antigen expression, which could be due to structural defects or deregulation affecting different components of the complex HLA class II APM and/or from lack of cytokine(s) in the tumor microenvironment. In this review, we have summarized the information about HLA class II antigen distribution in normal tissues, the structural organization of the HLA class II APM, their expression and regulation in malignant cells, the defects, which have been identified in malignant cells, and their functional and clinical relevance.

show abstract

“…13,14 However, the significance of these findings is controversial as some studies suggested DR expression on breast tumor cells is associated with favorable prognostic indicators such as well-differentiated tumors 15,16 and hormone receptor expression, 17 while others found no effect. 13,18 Similarly, tumor cell DR was positively associated with T-cell infiltration in some studies 19,20 and unrelated in others.…”

mentioning

confidence: 99%

“…13,18 Similarly, tumor cell DR was positively associated with T-cell infiltration in some studies 19,20 and unrelated in others. 16,21 Interpretation of the above studies may have been hampered by the fact that generic and not allelic DR expression was examined. This was likely because of the paucity of allotype-specific antibodies and the large number of DRB1 alleles, most of which are in linkage with additional structural DRB genes.…”

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

View full text Add to dashboard Cite

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...

show abstract

Different Patterns of Hla‐dr Antigen Expression in Normal Epithelium, Hyperplastic and Neoplastic Malignant Lesions of the Breast

Cited by 33 publications

References 32 publications

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

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

Contact Info

Product

Resources

About