Expression of HLA-D subloci DR and DQ by breast carcinomas is correlated with distinct parameters of favourable prognosis

Brunner, Christina; Gokel, J. M.; Riethmüller, Gert; Johnson, Judith P.

doi:10.1016/0277-5379(91)90374-m

Cited by 38 publications

(15 citation statements)

References 32 publications

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“…Discordant findings regarding the levels of HLA-DR expression were reported in breast cancer (Natali et al, 1983;Bernard et al, 1984;Hurlimann and Saraga, 1985;Bartek et al, 1987;Walker, 1987, 1988;Koretz et al, 1989;Moller et al, 1989;Brunner et al, 1991;Concha et al, 1991;Lucin et al, 1994). Furthermore, in breast cancer, the extent of HLA-DR expression appears to be related to tumor grade.…”

Section: Distribution Of Hla-dr Antigens In Solid Malignanciesmentioning

confidence: 70%

“…Furthermore, in breast cancer, the extent of HLA-DR expression appears to be related to tumor grade. 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%

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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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Section: Distribution Of Hla-dr Antigens In Solid Malignanciesmentioning

confidence: 70%

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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“…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.…”

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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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“…Dysregulation of class II expression in normal tissues has been implicated in the pathogenesis of autoimmune thyroiditis and diabetes [10], the hypothesis being that aberrant HLA-DR expression enhances antigen presentation by non-professional APC and engenders a pathological local immune response. In tumours, class II expression has been studied in a range of different neoplasms, including breast, prostatic, lung and colorectal cancers [11][12][13][14], and some evidence suggests that expression is more commonly found in lower grade tumours, with reduced metastatic potential. This is thought to relate to a containing effect of the local immune response.…”

Section: Discussionmentioning

confidence: 99%

A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production

Davies

Cope

Schofield

et al. 1995

Clinical and Experimental Immunology

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SUMMARY Patients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre‐ and postoperatively for cytokine studies. In vitro production of IL‐2, IL‐2R, IL‐1β, IL‐6 and TNF‐α by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. Plasma IL‐2R and IL‐6, and IL‐6 and TNF‐α production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing postoperatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL‐6, IL‐6R and TNF‐α, and expressed HLA class II. IL‐6 and TNF‐ α mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL‐6, and IL‐2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.

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Expression of HLA-D subloci DR and DQ by breast carcinomas is correlated with distinct parameters of favourable prognosis

Cited by 38 publications

References 32 publications

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

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

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

A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production

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