Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study

Reimers, Marlies S.; Engels, C.C.; Putter, Hein; Morreau, Hans; Liefers, G.J.; Velde, Cornelis J.H. van de; Kuppen, Peter J. K.

doi:10.1186/1471-2407-14-486

Cited by 77 publications

(93 citation statements)

References 54 publications

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“…In addition, increased HLA-E mRNA transcript levels in RCC lesions were associated with a worse prognosis of RCC patients [28] and thus might have a predictive value in tumor progression of this disease. This is in line with reports on breast and ovarian cancer, where HLA-G or HLA-E expression correlated with a worse overall and event-free survival [15] and also in rectal and colon cancers, in which a combination of the immune-related markers HLA class I, HLA-G, HLA-E and FoxP3 reflect an immune escape mechanism [29, 30]. Using qPCR, flow cytometry and/or immunohistochemistry (IHC) this study analyzed the expression of HLA-E in RCC cell lines as well as in RCC lesions and correlated these data with clinical and immunologic parameters.…”

Section: Introductionsupporting

confidence: 91%

HLA-E expression and its clinical relevance in human renal cell carcinoma

et al. 2016

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The non-classical human leukocyte antigen E (HLA-E) expression is frequently overexpressed in tumor diseases, transplants and virus-infected cells and represents an immunomodulatory molecule by binding to the receptors CD94/NKG2A, -B and –C on NK and T cells. Due to its immune suppressive features HLA-E expression might represent an important mechanism of tumors to escape immune surveillance.While an aberrant expression of the non-classical HLA-G antigen in human renal cell carcinoma (RCC) has been demonstrated to be associated with a worse outcome of patients and reduced sensitivity to immune effector cell-mediated cytotoxicity, the expression and function of HLA-E has not yet been analyzed in this tumor entity.Higher levels of HLA-E transcripts were detected in all RCC cell lines and tumor lesions, which were tested in comparison to normal kidney epithelium. Immunohistochemical staining of a tissue microarray (TMA) using the HLA-E-specific monoclonal antibody TFL-033 recognizing the cytoplasmic HLA-E α-chain as monomer revealed a heterogeneous HLA-E expression in RCC lesions with the highest frequency in chromophobe RCC when compared to other RCC subtypes. HLA-E expression did not correlate with the frequency of CD3+, CD4+, CD8+ and FoxP3+ immune cell infiltrations, but showed an inverse correlation with infiltrating CD56+ cells. In contrast to HLA-G, HLA-E expression in RCCs was not statistically significant associated with a decreased disease specific survival. These data suggest that HLA-E overexpression frequently occurs in RCC and correlates with reduced immunogenicity.

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Section: Introductionsupporting

confidence: 91%

HLA-E expression and its clinical relevance in human renal cell carcinoma

et al. 2016

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“…Moreover, our results showed that the expression level of ERO1-a was significantly correlated with the expression of MHC class I. Because many studies have demonstrated that low MHC class I expression is associated with poor prognosis (25)(26)(27), we are currently investigating whether low expression of ERO1-a correlates with poor prognosis. In conclusion, the cancer-associated ERO1-a plays a pivotal role in the host's immune response via proper Ag presentation by MHC class I molecules within a hypoxic microenvironment.…”

Section: Discussionmentioning

confidence: 70%

Cancer-Associated Oxidase ERO1-α Regulates the Expression of MHC Class I Molecule via Oxidative Folding

Kukita

Tamura

Tanaka

et al. 2015

The Journal of Immunology

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ERO1-α is an oxidizing enzyme that exists in the endoplasmic reticulum and is induced under hypoxia. It reoxidizes the reduced form of protein disulfide isomerase that has oxidized target proteins. We found that ERO1-α is overexpressed in a variety of tumor types. MHC class I H chain (HC) has two disulfide bonds in the α2 and α3 domains. MHC class I HC folding is linked to the assembly of MHC class I molecules because only fully disulfide-bonded class I HCs efficiently assemble with β2-microglobulin. In this study, we show that ERO1-α associates with protein disulfide isomerase, calnexin, and immature MHC class I before being incorporated into the TAP-1–associated peptide-loading complex. Importantly, ERO1-α regulates the redox state as well as cell surface expression of MHC class I, leading to alteration of susceptibility by CD8+ T cells. Similarly, the ERO1-α expression within cancer cells was associated with the expression level of MHC class I in colon cancer tissues. Thus, the cancer-associated ERO1-α regulates the expression of the MHC class I molecule via oxidative folding

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“…2016 (42) FCM, flow cytometry; ELISA, enzyme-linked immunosorbent assay; IHC, immunohistochemistry in this study [88]. Recently, our group explored HLA-G expression in patients with H. pylori infection and gastric cancer.…”

Section: (41)mentioning

confidence: 99%

HLA-G: Facts and Fictions

Shahraki

Alavianmehr

Farjadian

2018

Asian Pac J Cancer Biol

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Human leukocyte antigen (HLA)-G is a nonclassical MHC class I molecule with modulatory effects on NK and T cells. Unlike classical HLA class I molecules, HLA-G has seven isoforms, three of which are soluble. Soluble HLA-G molecules are reportedly able to transduce negative signals to immune cells after interacting with their corresponding receptors. The expression of these molecules plays significant roles in maternal tolerance against semi-allogenic fetuses. Overexpression of HLA-G in tumors and increased serum levels of soluble HLA-G have been reported in different malignancies, and these changes may be involved in tumoral immune evasion and cancer progression. To improve immune responses against tumor cells, the downmodulation of HLA-G by siRNA or blocking monoclonal antibodies can be helpful in cancer immunotherapy. Additionally, HLA-G can be considered a potential biomarker for the diagnosis and/or prognosis of certain cancers. Although polymorphism of the HLA-G gene-coding region is more limited than in classical HLA class I, some genetic variations in regulatory regions of the gene control the expression level of this molecule. Furthermore, epigenetic factors such as infections may affect the expression of HLA-G in infection-related cancers.

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Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study

Cited by 77 publications

References 54 publications

HLA-E expression and its clinical relevance in human renal cell carcinoma

HLA-E expression and its clinical relevance in human renal cell carcinoma

Cancer-Associated Oxidase ERO1-α Regulates the Expression of MHC Class I Molecule via Oxidative Folding

HLA-G: Facts and Fictions

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