Lacking prognostic significance of β2-microglobulin, MHC class I and class II antigen expression in breast carcinomas

Wintzer, H. O.; Benzing, M.; Kleist, S. von

doi:10.1038/bjc.1990.280

Cited by 47 publications

(24 citation statements)

References 54 publications

(41 reference statements)

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“…Following this line of argument it was tempting to speculate that tumours lacking the above antigens would be prone to pursue a more unfavourable clinical course as compared with those with normal expression. This idea was further strengthened by the association of MHC class I loss with a poorer degree of differentiation as reported for breast (Wintzer et al, 1990), colon (Momburg et al, 1986) and laryngeal (Lopez-Nevot et al, 1989) (Wintzer et al, 1990;Concha et al, 1991).…”

Section: Discussionmentioning

confidence: 85%

“…There is an ever increasing body of evidence that suggests that surface MHC class I antigen expression is altered on human tumours, in the sense of a loss or down-regulation of these molecules (Orgad et al, 1985;Festenstein and Garrido, 1986;Rees et al, 1988;Lopez-Nevot et al, 1989;Wintzer et al, 1990;Goepel et al, 1991). Recently similar findings were also described regarding the immunophenotype of TAP-1 in cervical and colorectal tumours (Cromme et al, 1994;Kaklamanis et al, 1994).…”

mentioning

confidence: 99%

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Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer

Korkolopoulou

Kaklamanis²,

Pezzella³

et al. 1996

Br J Cancer

164

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Summary Presentation of endogenous antigenic peptides to cytotoxic T lymphocytes is mediated by the major histocompatibility complex (MHC) class I molecules. For the stable assembly of MHC class I complex it is necessary that the antigenic peptide is transported by the MHC-encoded transporters TAP-1 and TAP-2 into a pre-Golgi region. T-cell-mediated host-vs-tumour response might therefore depend on the presence of these molecules on tumour cells. The presence of MHC class I antigens and TAP-1 was studied in a series of 93 resection specimens of non-small-cell lung carcinomas (NSCLCs) by immunohistochemical methods using antibodies against the assembled class I molecule, beta2-microglobulin (02-m), heavy-chain A locus, A2 allele and TAP-1 protein. Eighty-six patients were included in the survival analysis. Total loss of class I molecule was observed in 38% of the cases and was usually accompanied by loss of ,2-m and of heavy chain A locus. Selective loss of A locus was seen in 8.3% and of A2 allele in 27% of the cases. TAP-1 loss was always combined with P2-m and/or heavy chain A locus loss. No correlation was found between the expressional status of any of the above molecules, including the selective A2 allelic loss and histological type, degree of differentiation, tumoral stage, nodal stage and survival. Our findings suggest that loss of antigen-presenting molecules (including both MHC class I alleles and TAP-1) is a frequent event in lung cancer. However, the immunophenotypic profile of MHC class I and TAP-1 seems to be unrelated in vivo to the phenotype, growth or survival of NSCLC.

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Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer

Korkolopoulou

Kaklamanis²,

Pezzella³

et al. 1996

Br J Cancer

164

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“…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. 16,21 Interpretation of the above studies may have been hampered by the fact that generic and not allelic DR expression was examined.…”

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confidence: 93%

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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“…In fact, two studies reported that none of the breast carcinomas that were negative or only focally positive for HLA-DR expression were well differentiated (Zuk and Walker, 1988;Brunner et al, 1991); in addition, high levels of HLA-DR antigens expression were detected on primary medullary breast carcinoma which is usually associated with a relatively favorable prognosis (Natali et al, 1983;Bartek et al, 1987;Yazawa et al, 1993;Feinmesser et al, 2000;Lazzaro et al, 2001). In spite of these evidences, a number of studies failed to support a prognostic relevance of HLA-DR antigens in breast cancer (Perez et al, 1986;Wintzer et al, 1990;Lucin et al, 1994).…”

Section: Distribution Of Hla-dr Antigens In Solid Malignanciesmentioning

confidence: 99%

Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?

et al. 2003

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Intracellular signals, delivered in professional antigenpresenting cells following the engagement of major histocompatibility complex (MHC) class II molecules, activate a variety of cellular functions that also contribute to efficient antigen presentation. As far as human malignancies, the signaling ability of human leukocyte antigens (HLA) class II molecules is a rather wellcharacterized event in hematologic tumors; in contrast, very limited evidences are available in solid neoplasias of different histotypes that may constitutively express HLA class II antigens. Among solid malignancies, a significant proportion of human cutaneous melanomas have been shown to express HLA class II molecules, and cutaneous melanoma undoubtedly represents a 'model disease' to investigate tumor immunobiology, to unveil the molecular basis underlying the interactions between neoplastic cells and host's immune system, and ultimately to set up new bio-immunotherapeutic approaches. Upcoming preclinical evidences unveil a signaling potential of HLA-DR antigens expressed on melanoma cells, and suggest for the clinical implication of HLA class II molecules as novel therapeutic targets. Therefore, in this review, we will focus on the emerging role of HLA class II antigens as intracellular signal transducing elements in neoplastic cells of the melanocytic lineage, emphasizing their foreseeable role in targeted therapy of human melanoma and potentially of HLA class II antigens-positive tumors of different histology.

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Lacking prognostic significance of β2-microglobulin, MHC class I and class II antigen expression in breast carcinomas

Cited by 47 publications

References 54 publications

Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer

Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer

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

Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?

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