A meta-analysis of the impact of human leukocyte antigen-G on the outcomes of IVF/ICSI

BackgroundThe prognostic value of human leukocyte antigen G (HLA-G) expression in gastrointestinal (GI) cancers remains controversial. Thus, this meta-analysis aimed to summarize available evidence from case-control or cohort studies that evaluated this association.MethodsThe PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant studies written in English published up to April 1, 2021, and with no initial date. Furthermore, the Google Scholar and Google databases were also searched manually for gray literature. The protocol for this meta-analysis was registered at PROSPERO (CRD42020213411). Pooled hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for end points using fixed- and random-effects statistical models to account for heterogeneity. Publication bias was evaluated using a funnel plot, Begg’s and Egger’s tests, and the “trim and fill” method.ResultsA total of 30 eligible articles with 5737 unique patients, including 12 studies on colorectal cancer (CRC), 6 on gastric cancer (GC), 5 on esophageal cancer (ESCC), 5 on hepatocellular carcinoma (HCC), and 2 on pancreatic adenocarcinoma (PC), were retrieved. Both univariate (HR = 2.01, 95% CI: 1.48 ~ 2.72) and multivariate (HR = 2.69, 95% CI: 2.03 ~ 3.55) analyses revealed that HLA-G expression was significantly correlated with poor overall survival (OS), regardless of the cancer type or antibody used. Subgroup analysis stratified by antibody showed that the 4H84 (I2 = 45.8%, P = 0.101) antibodies could be trustworthy and reliable for detecting HLA-G expression in GI cancers. In addition, HLA-G expression was found to be correlated with adverse clinicopathological parameters such as clinical stage, nodal status, metastasis, and histological grade but not tumor status.ConclusionElevated HLA-G expression indicates a poor prognosis for GI cancer patients, and screening for this marker could allow for the early diagnosis and treatment of GI cancers to improve survival rates.

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Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis

The Pharmacogenomics Journal ◽

10.1038/s41397-021-00247-3 ◽

2021 ◽

Author(s):

Chonlaphat Sukasem ◽

Suthida Sririttha ◽

Chonlawat Chaichan ◽

Thapanat Nakkrut ◽

Patompong Satapornpong ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Antiepileptic Drugs ◽

Meta Analysis ◽

Strong Association ◽

Human Leukocyte ◽

Stevens Johnson Syndrome ◽

Thai Population ◽

Leukocyte Antigen ◽

Maculopapular Eruption ◽

Sequence Specific Oligonucleotide Probe

AbstractAromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41–3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77–9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

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Expression of human leukocyte antigen-G in systemic lupus erythematosus

Human Immunology ◽

10.1016/j.humimm.2007.11.001 ◽

2008 ◽

Vol 69 (1) ◽

pp. 9-15 ◽

Cited By ~ 33

Author(s):

Silvia Rosado ◽

Gema Perez-Chacon ◽

Susana Mellor-Pita ◽

Inmaculada Sanchez-Vegazo ◽

Carmen Bellas-Menendez ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Human Leukocyte Antigen ◽

Lupus Erythematosus ◽

Human Leukocyte ◽

Systemic Lupus ◽

Leukocyte Antigen ◽

Human Leukocyte Antigen G

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Human Herpesvirus 6A and 6B inhibit in vitro angiogenesis by induction of Human Leukocyte Antigen G

Scientific Reports ◽

10.1038/s41598-018-36146-0 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 4

Author(s):

Roberta Rizzo ◽

Maria D’Accolti ◽

Daria Bortolotti ◽

Francesca Caccuri ◽

Arnaldo Caruso ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Human Herpesvirus ◽

Human Leukocyte ◽

Leukocyte Antigen ◽

Human Leukocyte Antigen G ◽

In Vitro Angiogenesis

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Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-003050 ◽

2021 ◽

Vol 9 (10) ◽

pp. e003050

Author(s):

Chia-Ing Jan ◽

Shi-Wei Huang ◽

Peter Canoll ◽

Jeffrey N Bruce ◽

Yu-Chuan Lin ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Natural Killer ◽

Solid Tumors ◽

Low Dose ◽

Human Leukocyte ◽

Leukocyte Antigen ◽

Low Dose Chemotherapy ◽

Human Leukocyte Antigen G

BackgroundImmunotherapy against solid tumors has long been hampered by the development of immunosuppressive tumor microenvironment, and the lack of a specific tumor-associated antigen that could be targeted in different kinds of solid tumors. Human leukocyte antigen G (HLA-G) is an immune checkpoint protein (ICP) that is neoexpressed in most tumor cells as a way to evade immune attack and has been recently demonstrated as a useful target for chimeric antigen receptor (CAR)-T therapy of leukemia by in vitro studies. Here, we design and test for targeting HLA-G in solid tumors using a CAR strategy.MethodsWe developed a novel CAR strategy using natural killer (NK) cell as effector cells, featuring enhanced cytolytic effect via DAP12-based intracellular signal amplification. A single-chain variable fragment (scFv) against HLA-G is designed as the targeting moiety, and the construct is tested both in vitro and in vivo on four different solid tumor models. We also evaluated the synergy of this anti-HLA-G CAR-NK strategy with low-dose chemotherapy as combination therapy.ResultsHLA-G CAR-transduced NK cells present effective cytolysis of breast, brain, pancreatic, and ovarian cancer cells in vitro, as well as reduced xenograft tumor growth with extended median survival in orthotopic mouse models. In tumor coculture assays, the anti-HLA-G scFv moiety promotes Syk/Zap70 activation of NK cells, suggesting reversal of the HLA-G-mediated immunosuppression and hence restoration of native NK cytolytic functions. Tumor expression of HLA-G can be further induced using low-dose chemotherapy, which when combined with anti-HLA-G CAR-NK results in extensive tumor ablation both in vitro and in vivo. This upregulation of tumor HLA-G involves inhibition of DNMT1 and demethylation of transporter associated with antigen processing 1 promoter.ConclusionsOur novel CAR-NK strategy exploits the dual nature of HLA-G as both a tumor-associated neoantigen and an ICP to counteract tumor spread. Further ablation of tumors can be boosted when combined with administration of chemotherapeutic agents in clinical use. The readiness of this novel strategy envisions a wide applicability in treating solid tumors.

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