HLA-G Expression in Human Breast Cancer: Implications for Diagnosis and Prognosis, and Effect on Allocytotoxic Lymphocyte Response After Hormone Treatment In Vitro

He, Xu; Dong, Di; Yie, Shang-mian; Zhang, Pengcheng; Cao, Ming; Ye, Shang-rong; Li, Ke; Liu, Ji; Chen, Jie

doi:10.1245/s10434-009-0891-9

Cited by 94 publications

(100 citation statements)

References 28 publications

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“…24,25 Also, breast cancer patients with HLA-G-positive expression had a shorter disease-free survival time. 28 Other studies also revealed that there was significant correlation between HLA-G expression and poor clinical outcomes in lung, gastric and colorectal tumors. 26,31,32 In the context of ESCC, a previous study revealed that HLA-G was expressed in 90.9% (110/121) of the primary sites of ESCC, which is much higher than that observed in our study (65.8%, 52/79).…”

Section: Discussionmentioning

confidence: 97%

“…43 In our study, no correlation was found for the sHLA-G in plasma with clinicopathological parameters in ESCC patients. Similarly, no clinical significance for the sHLA-G was also observed in other malignancies such as breast cancer and renal cell carcinoma, 28,44 raising the hypothesis that the clinical relevance of sHLA-G is tumor type dependent and varies among different types of malignancies.…”

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.…”

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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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Section: Discussionmentioning

confidence: 97%

Section: Tumor Immunologymentioning

confidence: 99%

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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“…Among these studies, there is a high frequency of tumor cell-surface HLA-G expression with an absence in healthy tissue, and increased sHLA-G levels has been detected in various body fluids in a variety of cancers (14). Expression of HLA-G was found to be correlated with clinical parameters such as more advanced disease stage, tumor metastasis and/or with a worse prognosis in tumor patients, indicating that HLA-G could facilitate tumor immune escape, invasiveness and metastasis; thereby HLA-G expression was found to be associated with advanced clinical stage and disease progression and HLA-G expression was also documented as an unfavorable prognostic factor for many kinds of solid malignancies, including breast cancer (59)(60)(61)(62)(63)(64), colorectal cancer (65,66), cervical cancer (67,68), endometrial of allogeneic skin graft survival (52). In an immunocompetent HLA-G1 + M8…”

Section: Relevance Of Hla-g Expression In Cancersmentioning

confidence: 99%

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

Lin

Yan

2015

Mol Med

104

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Aberrant induction of human leukocyte antigen-G (HLA-G) expression has been observed in various malignancies and is strongly associated with tumor immune escape, metastasis and poor prognosis. To date, great achievements have been made in understanding the underlying mechanisms of HLA-G involved in tumor progression. HLA-G could lead to tumor evasion by inhibition of immune cell cytolysis, differentiation and proliferation and inhibition of cytokine production, induction of immune cell apoptosis, generation of regulatory cells and expansion of myeloid-derived suppressive cells and by impairment of chemotaxis. Moreover, HLA-G could arm tumor cells with a higher invasive and metastatic potential with the upregulation of tumor-promoting factor expression such as matrix metalloproteinases (MMPs), indicating that ectopic HLA-G expression could render multiple effects during the progression of malignancies. In this review, we summarized the mechanisms of HLA-G involved in promoting tumor cell immune escaping, metastasis and disease progression. Special attention will be paid to its significance as an attractive therapeutic target in cancers.

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“…1E-F); these results agree with those previously reported. 23 However, de Kruijf et al published that HLA-G expression had no significant prognosis correlation in breast cancer. 17 This discrepancy could be due to differences in the classification method of HLA-G expression.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy

et al. 2016

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(2016) Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy, OncoImmunology, 5:6, e1169356 ABSTRACTTumor immune escape has been a major problem for developing effective immunotherapy. The human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule whose primary function is to protect the fetus from the mother's immune system. While HLA-G is hardly found in normal adult tissues, various tumor cells are known to express it, aiding their escape from the immune system. Thus, HLA-G is an attractive immunotherapy target. CD4 C helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8 C cytotoxic T lymphocytes (CTLs) or by displaying direct antitumor effects. We report here that HLA-G expression in breast cancer significantly correlates with a poor prognosis. Also, we describe that the MHC class II-binding peptide HLA-G 26-40 was effective in eliciting tumor-reactive CD4 C T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2 0 -deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G 26-40 -specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.

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HLA-G Expression in Human Breast Cancer: Implications for Diagnosis and Prognosis, and Effect on Allocytotoxic Lymphocyte Response After Hormone Treatment In Vitro

Abstract: Our findings suggest that HLA-G may have potential clinical implications in diagnosis, prognosis, and immunotherapy of patients with breast cancer.

Cited by 94 publications

References 28 publications

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

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

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy

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