Prognostic relevance of soluble human leukocyte antigen–G and total human leukocyte antigen class I molecules in lung cancer patients

Schütt, Philipp; Schütt, Birgit; Switala, Magdalena; Bauer, Sebastian; Stamatis, Georgios; Opalka, Bertram; Eberhardt, Wilfried; Schüler, Martin; Horn, Peter A.; Rebmann, Vera

doi:10.1016/j.humimm.2010.02.015

Cited by 60 publications

(48 citation statements)

References 45 publications

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“…As a result, although sHLA-G levels are more elevated in patients with cancer than in healthy individuals, further studies are necessary to analyze its discriminatory value in relation to benign diseases. sHLA-G plasma levels are significantly elevated in patients with non-small cell lung cancer (56). HLA-G assay, either in biologic fluids or in biopsies, may have a clinical value in diagnosis, staging, or prognosis of cancer, but a prospective validation study should be conducted in order to use it as a biomarker.…”

Section: Hla-g As a Diagnostic And Prognostic Biomarkermentioning

confidence: 99%

“…An experimental approach to target HLA-G-expressing cells in a renal cell carcinoma model was the use of HLA-Gderived peptides based on the binding motif to the HLA-A24 (56). HLA-G peptides may induce a cytotoxic attack against HLA-G-expressing HLA-A24 tumor cells, suggesting that HLA-G-mediated suppression can be overcome using peptide-derived immunotherapy (57).…”

Section: Peptidesmentioning

confidence: 99%

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Molecular Pathways: Human Leukocyte Antigen G (HLA-G)

Curigliano

Criscitiello

Gelao

et al. 2013

Clinical Cancer Research

109

108

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Human leukocyte antigen G (HLA-G) is a nonclassical MHC class I molecule that exerts important tolerogenic functions. Its main physiologic expression occurs in the placenta, where it participates in the maternal tolerance toward the fetus. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. It is expressed in various types of primary solid (melanoma, head and neck, lung, urogenital, gastrointestinal, and breast cancers) and hematologic malignancies (acute leukemia, lymphomas) and metastases. HLA-G ectopic expression is observed in cancer, suggesting that its expression is one strategy used by tumor cells to escape immune surveillance. In this review, we will focus on HLA-G expression in cancers and its association with the prognosis. We will highlight the underlying molecular mechanisms of impaired HLA-G expression, the immune tolerant function of HLA-G in tumors, and the potential diagnostic use of membrane-bound and soluble HLA-G as a biomarker to identify tumors and to monitor disease stage. As HLA-G is a potent immunoinhibitory molecule, its blockade remains an attractive therapeutic strategy against cancer.

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Section: Hla-g As a Diagnostic And Prognostic Biomarkermentioning

confidence: 99%

Section: Peptidesmentioning

confidence: 99%

Molecular Pathways: Human Leukocyte Antigen G (HLA-G)

Curigliano

Criscitiello

Gelao

et al. 2013

Clinical Cancer Research

109

108

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“…We recently reported that sHLA-G in plasma from NSCLC patients were markedly higher than that in normal controls, which was significantly associated with the disease stages and patient survival. 15 A study by Schütt et al 27 showed that sHLA-G in plasma was exclusively elevated in NSCLC, especially in patients with SCC, and that patients with sHLA-G < 40 ng/ml had prolonged overall survival. sHLA-G was significantly higher in patients with neuroblastoma who developed a local or disseminated relapse than in those who remained in remission over a 3-6-year follow-up.…”

Section: Tumor Immunologymentioning

confidence: 99%

“…Interestingly, combination of sHLA-G and sHLA I and CEA was found to be a better prognosis factor than single markers alone in lung cancer, colorectal cancer, and multiple myeloma, respectively. 27,48,50 Future studies may determine whether a combination of selected secreted biomarkers including sHLA-G may provide a better approach in ESCC diagnosis and prognosis.…”

Section: Tumor Immunologymentioning

confidence: 99%

“…23 It has also been reported that the status of HLA-G expression or sHLA-G levels in plasma was correlated with certain clinicopathological parameters in malignancies such as hepatocellular carcinoma (HCC), 24,25 nonsmall-cell lung cancer (NSCLC), 15,26,27 breast cancer, 28 endometrial carcinoma, 29 B-cell chronic lymphocytic leukemia (B-CLL), 30 gastric carcinoma and colorectal cancer. 31,32 These studies indicated that HLA-G might serve as a clinical marker in the diagnosis or prediction of clinical outcomes for malignant diseases.…”

mentioning

confidence: 99%

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Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

Lin

Zhang

Zhou

et al. 2011

Intl Journal of Cancer

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Human leukocyte antigen (HLA)‐G inhibits functions of immune component cells and promotes malignant cells evading from antitumor immunity. We investigated the clinical relevance of HLA‐G expression in esophageal squamous cell carcinoma (ESCC). In our study, HLA‐G expression in 79 primary ESCC lesions and corresponding adjacent normal tissues were analyzed with immunohistochemistry. Soluble HLA‐G (sHLA‐G) in plasma was detected with enzyme‐linked immunosorbent assay (ELISA) in 41 ESCC patients (including 19 case‐matched lesions and plasma samples) and in 153 normal healthy controls. HLA‐G expression was observed in 65.8% (52/79) of the ESCC lesions but not in adjacent normal esophageal tissues. HLA‐G expression was more frequently observed in patients with advanced disease stage (III/IV vs. I/II, p = 0.01). Patients with HLA‐G expression had a significantly worse survival, and HLA‐G could be an independent prognostic factor. sHLA‐G levels in plasma were significantly increased in patients compared to normal controls (median: 152.4 U/ml vs. 8.9 U/ml, p < 0.001). The area under receiver‐operating characteristic (ROC) curve for sHLA‐G in plasma was 0.992. However, no significant correlation was found between sHLA‐G in plasma and clinical parameters studied. In conclusion, our findings indicated that HLA‐G expression in ESCC is associated with poor survival and could be a prognostic indicator. Furthermore, increased levels of sHLA‐G in plasma might be a useful preoperative biomarker for diagnosis.

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Soluble HLA-G is a differential prognostic marker in sequential colorectal cancer disease stages

et al. 2017

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The expression of HLA-G by tumour cells is an established mechanism to escape recognition and immune mediated destruction, allowing tumour survival, growth and metastasis. However, the prognostic value of soluble HLA-G (sHLA-G) remains unknown. Mucinous carcinoma (MC) is a distinct form of colorectal cancer (CRC) found in 10 to 15% of patients, which has long been associated with poor response to treatment. To investigate the prognostic value of plasma sHLA-G levels in CRC patients, preoperative plasma sHLA-G levels were determined by ELISA in CRC patients (n = 133). In addition, the local expression of HLA-G in tumour biopsies was assessed using tissue microarray analysis (n = 255). Within the high 33rd percentile of sHLA-G levels (265-890 U/mL; n = 44) we observed higher frequency of MC patients (p = 0.012; Chi-square), and higher sHLA-G levels in patients with vascular invasion (p = 0.035; two-tailed t-test). Moreover, MC patients had significantly higher sHLA-G levels compared to those with adenocarcinoma not otherwise specified (p = 0.036; two-tailed t-test). Surprisingly, while stage II patients showed negative correlation between sHLA-G levels and liver metastasis free survival (LMFS) (p = 0.041; R = -0.321), in stage III patients high sHLA-G levels were associated with significantly longer LMFS (p = 0.002), and sHLA-G levels displayed positive correlation with LMFS (p = 0.006; R = 0.409). High HLA-G expression in tumours was associated with poor cancer specific overall survival in stage II to III (p = 0.01), and with shorter LMFS in stage II patients (p = 0.004). Our findings reveal that sHLA-G levels are associated with distinct progression patterns in consecutive disease stages, indicating a potential value as surrogate marker in the differential prognosis of CRC.

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Prognostic relevance of soluble human leukocyte antigen–G and total human leukocyte antigen class I molecules in lung cancer patients

Cited by 60 publications

References 45 publications

Molecular Pathways: Human Leukocyte Antigen G (HLA-G)

Molecular Pathways: Human Leukocyte Antigen G (HLA-G)

Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

Soluble HLA-G is a differential prognostic marker in sequential colorectal cancer disease stages

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