Expression of HLA G in human tumors is not a frequent event

Real, Luis Miguel; Cabrera, Teresa; Collado, Antonia; Jiménez, Pilar; García, Ana Isabel Morales; Ruiz‐Cabello, Francisco; Garrido, Federico

doi:10.1002/(sici)1097-0215(19990517)81:4<512::aid-ijc2>3.0.co;2-o

Cited by 68 publications

(10 citation statements)

References 31 publications

(28 reference statements)

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“…It is assumed that upregulation helps the tumour to evade the immune response of the host by blocking NK cell activity whilst others dispute this [27, 31]. Improved survival of patients with epithelial ovarian cancer expressing HLA-G in tumour cells in ascites has been described [31].…”

Section: Discussionmentioning

confidence: 99%

“…Downregulation of classical HLA is associated with an unfavourable prognosis in ovarian cancer [25, 26]; however, the association of HLA-G with prognosis is controversial [12, 27–32]. Upregulation of HLA-G by IL6, IL8, or IL10 was suggested to help cancer cells evade the immune response by inhibition of NK cell- and CTL-mediated lysis [33–35].…”

Section: Introductionmentioning

confidence: 99%

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HLA-G Expression Is an Independent Predictor for Improved Survival in High Grade Ovarian Carcinomas

Rutten

Dijk

Savcı-Heijink

et al. 2014

Journal of Immunology Research

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Aberrant expression of human leukocyte antigens (HLA) class I has prognostic importance in various cancers. Here, we evaluated the prognostic value of classical (A/B/C) and nonclassical (G/E) HLA expression in 169 high grade epithelial ovarian cancer samples and linked that to clinicopathological characteristics and survival. Expression of HLA-A, -B/C, or -E was not correlated with survival. Survival was prolonged when tumours expressed HLA-G (P = 0.008) and HLA-G was an independent predictor for better survival (P = 0.011). In addition, HLA-G expression was associated with longer progression-free survival (P = 0.036) and response to chemotherapy (P = 0.014). Accordingly, high expression of HLA-G mRNA was associated with prolonged disease-free survival (P = 0.037) in 65 corresponding samples. Elevated serum-soluble HLA-G levels as measured by enzyme-linked immunosorbent assay in 50 matched patients were not correlated to HLA-G protein expression or gene expression nor with survival. During treatment, sHLA-G levels declined (P = 0.038). In conclusion, expression of HLA-G is an independent prognostic factor for improved survival in high grade epithelial ovarian cancer and a predictor for platinum sensitivity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HLA-G Expression Is an Independent Predictor for Improved Survival in High Grade Ovarian Carcinomas

Rutten

Dijk

Savcı-Heijink

et al. 2014

Journal of Immunology Research

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“…In addition, different researchers have shown that HLA-G mRNA expression does not systematically result in the presence of the protein [59,60]. This implies a tight post-transcriptional regulation of HLA-G gene expression.…”

Section: Discussionmentioning

confidence: 99%

A specific immune transcriptomic profile discriminates chronic kidney disease patients in predialysis from hemodialyzed patients

et al. 2013

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BackgroundChronic kidney disease (CKD) patients present a complex interaction between the innate and adaptive immune systems, in which immune activation (hypercytokinemia and acute-phase response) and immune suppression (impairment of response to infections and poor development of adaptive immunity) coexist. In this setting, circulating uremic toxins and microinflammation play a critical role. This condition, already present in the last stages of renal damage, seems to be enhanced by the contact of blood with bioincompatible extracorporeal hemodialysis (HD) devices. However, although largely described, the cellular machinery associated to the CKD- and HD-related immune-dysfunction is still poorly defined. Understanding the mechanisms behind this important complication may generate a perspective for improving patients outcome.MethodsTo better recognize the biological bases of the CKD-related immune dysfunction and to identify differences between CKD patients in conservative (CKD) from those in HD treatment, we used an high-throughput strategy (microarray) combined with classical bio-molecular approaches.ResultsImmune transcriptomic screening of peripheral blood mononuclear cells (1030 gene probe sets selected by Gene-Ontology) showed that 275 gene probe sets (corresponding to 213 genes) discriminated 9 CKD patients stage III-IV (mean ± SD of eGFR: 32.27±14.7 ml/min) from 17 HD patients (p < 0.0001, FDR = 5%). Seventy-one genes were up- and 142 down-regulated in HD patients. Functional analysis revealed, then, close biological links among the selected genes with a pivotal role of PTX3, IL-15 (up-regulated in HD) and HLA-G (down-regulated in HD). ELISA, performed on an independent testing-group [11 CKD stage III-IV (mean ± SD of eGFR: 30.26±14.89 ml/min) and 13 HD] confirmed that HLA-G, a protein with inhibition effects on several immunological cell lines including natural killers (NK), was down-expressed in HD (p = 0.04). Additionally, in the testing-group, protein levels of CX3CR1, an highly selective chemokine receptor and surface marker for cytotoxic effector lymphocytes, resulted higher expressed in HD compared to CKD (p < 0.01).ConclusionTaken together our results show, for the first time, that HD patients present a different immune-pattern compared to the un-dialyzed CKD patients. Among the selected genes, some of them encode for important biological elements involved in proliferation/activation of cytotoxic effector lymphocytes and in the immune-inflammatory cellular machinery. Additionally, this study reveals new potential diagnostic bio-markers and therapeutic targets.

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“…HLA-E, HLA-F and HLA-G mRNA detection from biopsies were further characterized by semi-quantitative PCR [49] using the Titan One Tube RT-PCR System (Roche Diagnostics, Heidelberg, Germany) and specific primers for HLA-G: G.257 (forward: 5′-GGAAGAGGAGACACGGAACA-3′) and G.1225 (reverse: 5′-TGAGACAGAGACGGAGACAT-3′) by Real et al, 1999 [51], T m 61°C and resulting PCR products were size fractionated on 1% ethidium bromide containing agarose gels [49]. For the detection of HLA-F the following PCR primers were applied: forward 5′-CAGTTCCCAGGTTCTAAAGTCC-3′ and reverse 5′-AACGTGTGCCTTTGGAGGA-3′.…”

Section: Methodsmentioning

confidence: 99%

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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Expression of HLA G in human tumors is not a frequent event

Cited by 68 publications

References 31 publications

HLA-G Expression Is an Independent Predictor for Improved Survival in High Grade Ovarian Carcinomas

HLA-G Expression Is an Independent Predictor for Improved Survival in High Grade Ovarian Carcinomas

A specific immune transcriptomic profile discriminates chronic kidney disease patients in predialysis from hemodialyzed patients

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

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