MHC antigens and tumor escape from immune surveillance

Garrido, Federico; Algarra, Ignacio

doi:10.1016/s0065-230x(01)83005-0

Cited by 273 publications

(194 citation statements)

References 154 publications

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“…Indeed, it is now known that the loss of MHC molecules is one of the mechanisms by which cancer cells escape host immunity (Garrido and Algarra, 2001). That most cells of B-cell lineage express HLA-DR, while those of T-cell lineage do not, may be one of the reasons for the difference in prognosis between B-cell and T-cell malignanciesthat is, leukaemias or lymphomas involving B-cell lineage generally have better prognoses than their T-cell counterparts.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-γ in haematopoietic tumour cells

et al. 2004

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By presenting immunogenic peptides at the cell surface, major histocompatibility complex (MHC) class II molecules play a key role in the control of adaptive immune responses. Whether expressed constitutively or induced by interferon-g, expression of MHC class II molecules is regulated via coactivator class II transactivator (CIITA); moreover, suppression of their expression is one mechanism by which cancer cells escape host immunity. In this study, we surveyed the relationship between the expression of one MHC class II antigen, HLA -DR, and its coactivators in a group of haematopoietic cell lines, and explored the role of the aberrant DNA methylation in silencing HLA-DR expression. Among 26 cell lines studied, HLA-DR expression was lost from eight T-cell and two myeloid leukaemia cell lines, and this loss was closely associated with suppression of CIITA-PIV expression. Notably, nine of the 10 cell lines that lost CIITA-PIV expression showed methylation of the gene's 5 0 CpG island. Thus, DNA methylation is believed to inhibit the expression of MHC class II molecules in haematopoietic tumour cells by silencing its coactivator, CIITA-PIV. Furthermore, methylation of CIITA-PIV was detected in seven of 32 primary acute myeloid leukaemia specimens, indicating that epigenetic alteration is not a cell line-specific phenomenon. Collectively, these data suggest that, by suppressing expression of MHC class II molecules, epigenetic inactivation of CIITA provides a survival advantage to a subset of haematopoietic tumours.

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Section: Discussionmentioning

confidence: 99%

Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-γ in haematopoietic tumour cells

et al. 2004

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“…Since CTLs recognize tumor antigens in the context of HLA class I molecules, alteration of HLA surface expression is a frequent mechanism used by tumors to evade T-cell control. [2][3][4] Different altered HLA class I phenotypes, including total loss or downregulation of HLA class I antigens, HLA haplotype, HLA locus or HLA allele, have been described for tumors originating from different tissues; and multiple molecular mechanisms have been identified as responsible for these changes. 3,4 Total lack of HLA class I antigen expression is frequently observed for tumor tissue and cultured tumor cell lines of malignant melanoma.…”

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confidence: 99%

“…[2][3][4] Different altered HLA class I phenotypes, including total loss or downregulation of HLA class I antigens, HLA haplotype, HLA locus or HLA allele, have been described for tumors originating from different tissues; and multiple molecular mechanisms have been identified as responsible for these changes. 3,4 Total lack of HLA class I antigen expression is frequently observed for tumor tissue and cultured tumor cell lines of malignant melanoma. 3,4 The molecular mechanisms causing this defect are heterogenous and can be of a reversible or an irreversible nature.…”

mentioning

confidence: 99%

“…3,4 Total lack of HLA class I antigen expression is frequently observed for tumor tissue and cultured tumor cell lines of malignant melanoma. 3,4 The molecular mechanisms causing this defect are heterogenous and can be of a reversible or an irreversible nature. An apparent HLA class I-negative phenotype, reversible by IFN-␥, can be due to regulatory defects leading to transcriptional downregulation of different components of the antigen-processing and presentation machinery.…”

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confidence: 99%

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Complete loss of HLA class I antigen expression on melanoma cells: A result of successive mutational events

Paschen

Méndez

Jiménez

et al. 2002

Intl Journal of Cancer

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Alterations in the surface expression of HLA class I molecules have been described as a strategy of tumors to evade recognition by cytotoxic T cells. We detected complete loss of HLA class I antigen presentation for 2 tumor cell lines from 1 melanoma patient, the first originated from a regional lymph node lesion diagnosed simultaneously with the primary tumor and the second established 8 months later from a metastatic pleural effusion sample. Antigen presentation was not inducible with IFN-␥ but could be restored after transfection of tumor cells with b2m cDNA, indicating a defect in b2m expression. Analysis of the nature of this defect revealed that it originated from at least 2 mutational events affecting both copies of the b2m gene: a microdeletion of 498 bp in one b2m gene, including its entire exon 1, and a macrodeletion involving the entire copy of the second b2m gene. Microsatellite analysis pointed to the macrodeletion by demonstrating LOH for several specific markers on the long arm (q) of chromosome 15. Structural imbalance of 15q was verified by FISH. FISH studies also indicated the coexistence of a structurally abnormal variant of chromosome 15q with 2 apparently entire chromosomes 15q harboring the homozygous b2m microdeletion. Block of b2m expression in tumor cells builds a barrier to immunotherapy of cancer patients, and its early incidence should be of major consideration in the development and design of immunotherapeutic strategies.

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“…This is probably because MHC class II and class II-restricted Ag presentation may be much more complex than that of MHC class I (11). Most solid tumor cell lines hardly express MHC class II Ags on their surfaces, because some tumor cells may lose expression of MHC class I and/or class II molecules for several reasons (12). Loss of MHC molecules is one of the major mechanisms for tumor cells to escape from immune surveillance.…”

Section: Linical Trials For Cancer Immunotherapy Have Recentlymentioning

confidence: 99%

Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas

Kanaseki¹,

Ikeda²,

Takamura³

et al. 2003

The Journal of Immunology

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In this study, we first categorized nine squamous cell carcinoma (SCC) cell lines into two groups in terms of the expression of HLA-DR, -DP, and -DQ molecules. Subsequently, the expression of class II transactivator (CIITA) was studied in these cell lines, because it is widely accepted that the expression of MHC class II molecules is regulated by different types of CIITA transcripts that are initiated by distinct promoters. The majority of the SCC cell lines (six of nine) expressed HLA-DR molecules and CIITA promoter IV (pIV) transcripts in the presence of IFN-γ. In contrast, three of the nine SCC cell lines were completely negative for class II molecules and all types of CIITA, suggesting epigenetic changes in the promoter region in these cells. Previously, methylation of CIITA pIV was reported to silence CIITA gene expression. We extensively studied the methylation status of CIITA pIV using a panel of 22 SCC cell lines. Remarkably, none of the SCC cell lines demonstrated hypermethylation at the site. In contrast, treatment with a histone deacetylation inhibitor in combination with IFN-γ clearly restored the expression of the CIITA type IV gene in the HLA-DR-negative SCC cell lines, and the acetylation status of histone H3 examined by chromatin immunoprecipitation analysis was closely associated with the gene expression. Moreover, stable transfection of the CIITA gene into an HLA-DR-negative cell line restored constitutive expression of MHC class II molecules. Therefore, histone deacetylation, but not hypermethylation, modifies CIITA DNA and class II gene expression in SCC.

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MHC antigens and tumor escape from immune surveillance

Cited by 273 publications

References 154 publications

Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-γ in haematopoietic tumour cells

Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-γ in haematopoietic tumour cells

Complete loss of HLA class I antigen expression on melanoma cells: A result of successive mutational events

Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas

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