HLA Antigen Changes in Malignant Tumors of Mammary Epithelial Origin: Molecular Mechanisms and Clinical Implications

Campoli, Michael; Chang, Chien‐Chung; Oldford, Sharon A.; Edgecombe, Allison; Drover, Sheila; Ferrone, Soldano

doi:10.3233/bd-2004-20112

Cited by 29 publications

(35 citation statements)

References 91 publications

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“…By contrast, it is higher than that in cutaneous basal cell, lung (i.e., squamous) and bladder carcinoma but lower than that in renal cell carcinoma. It is noteworthy that, in contrast to melanoma, in some tumors, such as breast [65], colon [6,37,66,74] and cervical [81] carcinoma, HLA class II antigen expression is not restricted to cells that have undergone malignant transformation. The high degree of variability regarding the frequency of HLA class II antigen expression in cutaneous and uveal melanoma lesions reported by the published studies parallels results obtained in other types of solid tumors for which more than 100 surgically removed primary lesions have been analyzed (FIGURE 3) [6,37, .…”

Section: Frequency Of Hla Class II Antigen Expressionmentioning

confidence: 95%

“…HLA-DP antigens appear to be detected more frequently than HLA-DQ antigens in metastases, but less frequently in primary lesions [7,18,19,28]. The differential expression of the HLA class II antigen gene products is not unique to melanoma cells, as it has also been described in leukemic cells [86,87], as well as in malignant cells derived from carcinomas of the breast [65], liver [37] and colon [6,37,66,74]. These findings contrast with the coordinated expression of HLA-DR, -DQ and -DP antigens on conventional APCs under basal conditions and on IFN-γ-treated endothelial cells and fibroblasts [26,27] and suggest abnormalities in the regulatory mechanisms that control HLA-DR, -DQ and -DP antigen expression by malignant cells.…”

Section: Frequency Of Hla Class II Antigen Expressionmentioning

confidence: 97%

“…Others that generally have not been taken into account in the design of the published studies, as well as in the analysis of the results, include characteristics of the patient population, tumor stage and histological type of melanoma lesion (e.g., acral-lentiginous, amelanotic, lentigo maligna, nodular, superficial spreading and uveal). The role of the latter variable is suggested by the differential frequency of HLA class II antigen expression in histological subtypes of uveal melanoma [58,64], as well as of a number of malignancies, including carcinoma of the breast [65], lung [37], colon [6,37,66,74] and ovary [78,83].…”

Section: Frequency Of Hla Class II Antigen Expressionmentioning

confidence: 99%

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A fresh look at an old story: revisiting HLA class II antigen expression by melanoma cells

Ferrone¹,

Campoli

2006

Expert Review of Dermatology

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The appearance of human leukocyte antigen (HLA) class II antigens may be associated with malignant transformation of melanocytes. However, the information available regarding the clinical relevance of HLA class II antigen expression, which has been found in approximately 50% of primary and metastatic cutaneous melanoma lesions, is scarce and conflicting. The debate regarding the clinical relevance of HLA class II antigen expression by malignant melanocytes, in conjunction with our increased understanding of HLA class II antigen processing and presentation, their role in the interactions between melanoma cells and components of the adaptive immune system and their potential involvement in melanoma cell migration have provided the impetus to revisit the topic of HLA class II antigen expression by malignant melanocytes. This review will discuss the current knowledge regarding HLA class II antigens, including the presentation pathway; frequency of expression in cell lines and lesions of melanocytic origin; potential molecular mechanisms involved in such expression; potential role in the biology of melanoma cells and their interaction with components of the adaptive immune system; and, lastly, the potential clinical significance of HLA class II antigen expression in melanoma lesions and the variables that may confound such assessment.Expert Rev. Dermatol. 1(6), 805-823 (2006) As in other types of cells in humans and in other animal species, malignant transformation of human melanocytes may be associated with changes in gene expression and in their antigenic profile [1]. Among the latter, changes in human leukocyte antigen (HLA) expression are of particular interest to tumor immunologists and clinical oncologists owing to the potential involvement of immunological events in the clinical course of melanoma [2] and owing to the crucial role played by HLA antigens in the interactions of tumor cells with the host's immune system [3][4][5][6]. Over the past 20 years, a number of studies have demonstrated that changes in HLA antigen expression occur frequently in melanoma lesions [1]. Most of these studies have focused on the analysis of HLA class I antigen expression by melanoma cells. This emphasis reflects the crucial role played by HLA class I antigens in the interactions of tumor cells with effector cells of the innate and adaptive immune system (i.e., CD8 + , HLA class I antigen-restricted, tumor antigen [TA]-specific cytotoxic T lymphocytes [CTLs] [3] and natural killer [NK] cells [4]). These studies have revealed that HLA class I antigen defects are found frequently in melanoma cells both in vitro and in vivo [1], and these defects are clinically significant [1], most likely because they provide tumor cells with a mechanism to escape immune cell recognition and destruction [1]. Interested readers are referred to recent reviews for additional information on HLA class I antigen defects in melanoma lesions and on their functional and clinical significance [1].Much less information is available regarding the functi...

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Section: Frequency Of Hla Class II Antigen Expressionmentioning

confidence: 95%

Section: Frequency Of Hla Class II Antigen Expressionmentioning

confidence: 97%

Section: Frequency Of Hla Class II Antigen Expressionmentioning

confidence: 99%

See 1 more Smart Citation

A fresh look at an old story: revisiting HLA class II antigen expression by melanoma cells

Ferrone¹,

Campoli

2006

Expert Review of Dermatology

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“…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.…”

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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“…Information about APM component expression in SCCHN lesions and in other types of tumors is scanty. Only a limited number of malignant lesions have been investigated by immunohistochemistry, and the analysis has been restricted to a few APM components in the majority of the studies (17,18). The paucity of information reflects, at least in part, the limited availability of mAb suitable for immunohistochemical detection of APM components in tissues and, especially, in formalin-fixed, paraffin-embedded tissue sections.…”

Section: Clinical Significance Of Abnormalities In Hla Class I Antigementioning

confidence: 99%

Immune Escape Associated with Functional Defects in Antigen-Processing Machinery in Head and Neck Cancer

Ferris

Whiteside

Ferrone

2006

Clinical Cancer Research

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131

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Recent revival of interest in the role of immune surveillance in the pathogenesis and control of malignant diseases has focused attention on escape mechanisms used by tumor cells to evade immune recognition. Defects in the host's tumor antigen^specific immune responses and abnormalities in tumor cell expression of HLA class I molecules and tumor antigen are known to contribute to tumor progression. However, the mechanism(s) responsible for the lack of tumor cell recognition by functional HLA class I antigen^restricted, tumor antigen^specific CTLs despite expression of the restricting HLA class I allele and targeted tumor antigen by tumor cells remain(s) unexplained. In squamous cell carcinomas of the head and neck (SCCHN), this type of tumor escape is a rule rather than the exception. Here, we discuss evidence pointing to functional defects in the antigen-processing machinery as one mechanism underlying resistance of SCCHN cells to recognition and lysis by HLA class I antigen^restricted, tumor antigen^specific CTL. In addition, based on the restoration by IFN-g of SCCHN cell sensitivity to recognition by these CTL, we suggest strategies that may improve the clinical course of the disease by enhancing susceptibility of malignant cells to immune recognition.

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HLA Antigen Changes in Malignant Tumors of Mammary Epithelial Origin: Molecular Mechanisms and Clinical Implications

Cited by 29 publications

References 91 publications

A fresh look at an old story: revisiting HLA class II antigen expression by melanoma cells

A fresh look at an old story: revisiting HLA class II antigen expression by melanoma cells

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

Immune Escape Associated with Functional Defects in Antigen-Processing Machinery in Head and Neck Cancer

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