CD4+ T lymphocytes infiltrating human breast cancer recognise autologous tumor in an MHC-class-II restricted fashion

Dadmarz, Roya; Sgagias, Magdalene K.; Rosenberg, Steven A.; Schwartzentruber, Douglas J.

doi:10.1007/bf01517229

Cited by 55 publications

(45 citation statements)

References 28 publications

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“…The GO analysis revealed that the DE genes were associated with mitogen-activated protein kinase phosphatase activity, major histocompatibility complex class II receptor activity and DNA metabolic processes, which is consis tent with previous research (36)(37)(38). Previous studies have demonstrated that signaling pathways, including the Ras, p53 and transforming growth factor-β signaling pathways, serve a critical role in the regulation of pathophysiological processes in ovarian cancer (39)(40)(41).…”

Section: Discussionsupporting

confidence: 85%

Microarray expression profiling of long non-coding RNAs in epithelial ovarian cancer

et al. 2017

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Abstract. Although numerous long non-coding RNAs (lncRNAs) have been identified to be important in human cancer, their potential regulatory roles in epithelial tumorigenesis and tumor progression in ovarian cancer remain unclear. The purpose of the present study was to investigate lncRNAs that were differentially expressed (DE) in epithelial ovarian cancer and to explore their potential functions. The lncRNA profiles in five pairs of human epithelial ovarian cancer tissues and their adjacent normal tissues were described using microarrays. The results of the microarray analysis revealed that 672 upregulated and 549 downregulated (fold-change ≥2.0) lncRNAs were DE between the cancerous and normal tissues. Reverse transcription-quantitative polymerase chain reaction was used to validate the microarray results using four upregulated (RP11-1C1.7, XLOC_003286, growth arrest-specific 5 and ZNF295-AS1) and four downregulated (protein tyrosine kinase 7, maternally expressed gene 3, AC079776.2 and ribosomal protein lateral stalk subunit P0 pseudogene 2) lncRNAs. Furthermore, gene ontology and pathway analyses were used to carry out functional analyses of the candidate genes of DE lncRNAs. The results identified lncRNAs with significantly altered expression profiles in human epithelial ovarian cancer cells compared with those in adjacent normal cells. These data offer new insights into the occurrence and development of epithelial ovarian cancer, and these lncRNAs may provide novel molecular biomarkers for further research on epithelial ovarian cancer.

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Section: Discussionsupporting

confidence: 85%

Microarray expression profiling of long non-coding RNAs in epithelial ovarian cancer

et al. 2017

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“…20 Both CD4 and CD8 T-cells have been reported to be specific cell types in ovarian cancer. 21,22 Consequently, HLAclass I as well as class II peptides is part of antitumoral immunology of ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

HLA‐class II haplotype associations with ovarian cancer

Kübler

Arndt

Wardelmann

et al. 2006

Intl Journal of Cancer

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The development of cancer is a multistep process that is characterized by the accumulation of genetic alterations in cells and changed cellular interactions with the surrounding healthy tissues. The human immune system is believed to be intrinsically involved in this process. The correlation of certain human leukocyte antigen (HLA)-class I and II haplotypes with tumorigenesis is documented in a variety of tumors. However, few data exist on the possible association of specific HLA-class II alleles or haplotypes with ovarian cancer. In our sample of 52 Caucasian patients with primary ovarian carcinoma and 239 female healthy local controls, we observed a significantly increased incidence of the HLA-class II haplotypes DRB1*0301 -DQA1*0501 -DQB1*0201 (p < 0

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Section: Abstract: Hla-dr Expression; Hla-drb Alleles; T-cell Infiltmentioning

confidence: 99%

“…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 expression of HLA class II in breast carcinoma generally concur that DR and its cochaperone invariant chain (Ii) are more often and more strongly upregulated than HLA-DP or DQ. 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.…”

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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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CD4+ T lymphocytes infiltrating human breast cancer recognise autologous tumor in an MHC-class-II restricted fashion

Cited by 55 publications

References 28 publications

Microarray expression profiling of long non-coding RNAs in epithelial ovarian cancer

Microarray expression profiling of long non-coding RNAs in epithelial ovarian cancer

HLA‐class II haplotype associations with ovarian cancer

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

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