Biological‐clinical significance of selective loss of HLA‐class‐I allelic product expression in squamous‐cell carcinoma of the uterine cervix

Honma, Shiho; Tsukada, Seiji; Honda, Shuji; Nakamura, Minoru; Takakuwa, Koichi; Maruhashi, T; Kodama, Shintaro; Kanazawa, Kazuki; Takahashi, Takeshi; Tanaka, Kenichi

doi:10.1002/ijc.2910570507

Cited by 39 publications

(26 citation statements)

References 20 publications

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“…In cervical cancer, tumour cells that have decreased expression of the HLA-B7 allele have been associated with a high propensity for lymph node metastases and a poorer clinical outcome (Honma et al, 1994;Ellis et al, 1995). It is thought that the expression of this allele may be important in the control of HPV-associated carcinoma, by playing a dominant role in the presentation of immunogenic HPV-derived peptides to cytotoxic T-cells (Ellis et al, 1995;Keating et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma

Vora

Rodgers²,

Aj³

et al. 1997

Br J Cancer

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Summary For the presentation of peptide antigens to cytotoxic CD8+ T lymphocytes of the immune system, the expression of human leukocyte antigen (HLA) class I molecules on the cell surface is necessary. There is increasing evidence that surface HLA class antigen expression is altered in a variety of human tumours by either loss or down-regulation of these molecules, which may be a strategy for evasion of immunosurveillance by malignant cells. This study has examined the expression of HLA class molecules in head and neck squamous cell carcinoma (HNSCC) specimens by immunohistochemistry, using a wide panel of antibodies directed against allele-specific as well as monomorphic determinants of these molecules. The expression of TAP proteins, HLA-DR and the co-stimulatory molecule ICAM-1 were also studied. In addition, the expression of the tumour-associated antigens (TAA) p53 and MAGE genes was determined. Aberrant allelic expression of HLA class antigens was detected in 17 out of 34 (50%) of the specimens stained, whereas HLA class I expression determined by W6/32 staining was found to be heterogeneous in only 2 out of 34 (6%) cases. Decreased expression of ICAM-1 was observed in 12 out of 34 (35%) tumour specimens and de novo expression of HLA-DR (HLA class 11) by carcinoma cells in 13 out of 34 (38%) cases. Aberrant expression of HLA class I antigens was frequently observed in cases in which MAGE genes and p53 overexpression were detected. The altered expression of these immunomodulatory molecules in HNSCC may affect prognosis and has important implications for peptide-based immunotherapy strategies for these patients.

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Section: Discussionmentioning

confidence: 99%

An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma

Vora

Rodgers²,

Aj³

et al. 1997

Br J Cancer

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“…It is interesting to speculate that these changes are the result of immunoselective influences in the natural history of cervical neoplasia. Indeed, there is evidence of an increased incidence of HLA class I down-regulation in cervical carcinoma lymph node metastases (Cromme et al, 1994b) and at an enhanced frequency for HLA-B7/40 (Honma et al, 1994). Even the loss of expression of a single MHC restriction element can allow a tumour to grow progressively (Seung et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression

Keating

Cromme²,

Duggan-Keen³

et al. 1995

Br J Cancer

151

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Summary The development of cervical carcinoma is strongly associated with specific types of human papillomaviruses (HPVs). A role for cellular immunity in cervical disease is supported by the increased occurrence of HPV-associated lesions in immunosuppressed individuals. Upon viral infection or malignant transformation, ensuing alterations in gene expression result in the generation of novel sets of peptides which can form complexes with specific HLA class I heavy chains and P2-microglobulin. These are then expressed at the cell surface as potential targets for specific T cells. In this study of 100 carcinomas HLA-A and -B class I expression by the tumour cells was down-regulated at one or more alleles in at least 73% of cervical carcinomas. Interference with the transporter associated with antigen presentation (TAP), which translocates cytosolic peptides from endogenously synthesised proteins (e.g. viral) into the lumen of the endoplasmic reticulum was found in 38% of the HLA class I down-regulated tumours. Loss of expression for common HLA class I alleles ranged from 36% to 71%, and such changes might be expected to influence specific immunogenic peptide presentation and consequent immune recognition. These results underline the importance of single as well as multiple allelic loss in cervical neoplasia and have important implications for attempts to intervene immunologically in cervical cancer.

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“…90 Approximately 70% of cervical carcinoma samples exhibit loss or downregulation of HLA-A or -B locus gene products and 17% of tumor specimens downregulation or loss of specific HLA-A and -B alleles (Table II). [91][92][93][94][95] These allelic losses correlate with the tumor-positive lymph node status, disease progression, and/or reduced patients' survival. Thus, HLA class I antigen alterations may contribute to the phenotype causing HPV-induced cervical carcinoma.…”

Section: Hla Class I Antigen Downregulationmentioning

confidence: 99%

Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation

Seliger

Ritz

Ferrone

2005

Intl Journal of Cancer

113

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In humans as in other animal species, CD81 cytotoxic T lymphocytes (CTLs) play an important if not the major role in controlling virus-infected and malignant cell growth. The interactions between CD81 T cells and target cells are mediated by human leukocyte antigen (HLA) class I antigens loaded with viral and tumor antigen-derived peptides along with costimulatory receptor/ligand stimuli. Thus, to escape from CD8 1 T-cell recognition and destruction, viruses and tumor cells have developed strategies to inhibit the expression and/or function of HLA class I antigens. In contrast, cells with downregulated MHC class I surface expression can be recognized by NK cells, although NK cell-mediated lysis could be abrogated by the expression of inhibiting NK cell receptors. This review discusses the molecular mechanisms utilized by viruses to inhibit the formation, transport and/or expression of HLA class I antigen/peptide complexes on the cell surface. The knowledge about viral interference with MHC class I antigen presentation is not only crucial to understand the pathogenesis of viral diseases, but contributes also to the design of novel strategies to counteract the escape mechanisms utilized by viruses. These investigations may eventually lead to the development of effective immunotherapies to control viral infections and virus-associated malignant diseases. ' 2005 Wiley-Liss, Inc.

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Biological‐clinical significance of selective loss of HLA‐class‐I allelic product expression in squamous‐cell carcinoma of the uterine cervix

Cited by 39 publications

References 20 publications

An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma

An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma

Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression

Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation

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