Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

Yang, Zhaozhong; Feng, Jia; Xiao, Li; Chen, Xi; Yao, Yuanfei; Li, Yiqun; Tang, Yu; Zhang, Shuai; Lü, Min; Yu, Qing; Wu, Hongjin; Shi, Ming

doi:10.1002/hep.30924

Cited by 29 publications

(25 citation statements)

References 35 publications

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“…Previous evidence has shown that PGLYRP2 is overexpressed in hepatocellular carcinoma (HCC) cells and can significantly strengthen the anti-tumor immune response in mice. Hence, tumor-derived PGLYRP2 is considered as a novel biomarker for HCC, and its potential in detecting cancer immunity and designing immunotherapies is highlighted [ 14 ]. In addition, PGLYRPs can regulate the sensitivity to inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Through hydrolyzing the amide bond between the N-acetylmuramic acid and L-Ala, PGLYRP2 separates the cross-linked bacterial peptidoglycans (PGN) and thus digests them into fragments. It is reported that PGLYRP2 is functional in tumor development, immune response in tumor microenvironment, infectious diseases, inflammatory responses and brain development [ 2 – 4 ]. To date, no studies have described the profile of PGLYRP2 in the case of SLE.…”

Section: Introductionmentioning

confidence: 99%

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PGLYRP2 as a novel biomarker for the activity and lipid metabolism of systemic lupus erythematosus

Meng

Jia

et al. 2021

Lipids Health Dis

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Background To assess the value of peptidoglycan recognition protein 2 (PGLYRP2) in assessing the disease activity and lipid metabolism in patients with systemic lupus erythematosus (SLE). Methods SLE patients with stable disease (n = 15), active lupus nephritis (LN) (n = 15) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (n = 15) admitted to Northern Jiangsu People’s Hospital (Jiangsu, China) in 2019–2020 were recruited. In addition, volunteers with matched age and sex (n = 15) were enrolled as controls. The level of PGLYRP2 in the serum and its expression in peripheral blood mononuclear cells (PBMCs) were measured. The link between PGLYRP2 level and clinical parameters (including lipid profile) was described. Results Serum PGLYRP2 level in SLE cases exceeded that in healthy volunteers (3938.56 ± 576.07 pg/mL), and significantly higher in active LN (5152.93 ± 446.13 pg/mL) and NP-SLE patients (5141.52 ± 579.61 pg/mL). As shown by quantitative real-time PCR results, the expression of PGLYRP2 in PBMCs of SLE patients with active LN and NP-SLE surpassed that in healthy volunteers (P < 0.01). Receiver operating characteristic (ROC) curves demonstrated that PGLYRP2 was capable of distinguishing stable SLE from active LN (AUC = 0.841, 95%CI = 0.722–0.960, P = 0.000). PGLYRP2 level positively correlated with SLEDAI of SLE patients (r = 0.5783, P < 0.01). Moreover, its level varied with serological and renal function parameters (complement 3, complement 4, estimated glomerular filtration rate and 24-h urine protein) and immunoglobulin A (IgA) of SLE. A potential correlation between PGLYRP2 level and lipid profile (HLD-c, Apo-A1 and Apo B/A1) was determined in SLE patients. The linear regression analysis indicated SLEDAI as an independent factor of PGLYRP2 level, with a positive correlation in between (P < 0.05). Conclusions Serum PGLYRP2 level significantly increases in SLE patients, and is positively correlated to SLEDAI. Moreover, serum PGLYRP2 level is correlated with renal damage parameters and the abnormal lipid profile of SLE. PGLYRP2 could be used to predict SLE activity, dyslipidemia and cardiovascular disease risks in SLE patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PGLYRP2 as a novel biomarker for the activity and lipid metabolism of systemic lupus erythematosus

Meng

Jia

et al. 2021

Lipids Health Dis

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“…Luciferase assays were performed as previously described (Yang et al, 2020). Briefly, HEK293T cells were transfected with control 5′ UTR, full-length, SL1 alone, or SL1-deleted SARS-CoV-2 5′ UTR luciferase reporter plasmid using FuGENE Transfection Reagent (Promega).…”

Section: Luciferase Assaymentioning

confidence: 99%

SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism

Shi

Wang

Fontana

et al. 2020

Preprint

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SUMMARYThe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host immunity and cellular defense. The SARS-CoV-2 nonstructural protein 1 (Nsp1) is known to inhibit host protein translation and could be a target for antiviral therapy against COVID-19. However, how SARS-CoV-2 circumvents this translational blockage for the production of its own proteins is an open question. Here, we report a bipartite mechanism of SARS-CoV-2 Nsp1 which operates by: (1) hijacking the host ribosome via direct interaction of its C-terminal domain (CT) with the 40S ribosomal subunit and (2) specifically lifting this inhibition for SARS-CoV-2 via a direct interaction of its N-terminal domain (NT) with the 5’ untranslated region (5’ UTR) of SARS-CoV-2 mRNA. We show that while Nsp1-CT is sufficient for binding to 40S and inhibition of host protein translation, the 5’ UTR of SARS-CoV-2 mRNA removes this inhibition by binding to Nsp1-NT, suggesting that the Nsp1-NT-UTR interaction is incompatible with the Nsp1-CT-40S interaction. Indeed, lengthening the linker between Nsp1-NT and Nsp1-CT of Nsp1 progressively reduced the ability of SARS-CoV-2 5’ UTR to escape the translational inhibition, supporting that the incompatibility is likely steric in nature. The short SL1 region of the 5’ UTR is required for viral mRNA translation in the presence of Nsp1. Thus, our data provide a comprehensive view on how Nsp1 switches infected cells from host mRNA translation to SARS-CoV-2 mRNA translation, and that Nsp1 and 5’ UTR may be targeted for anti-COVID-19 therapeutics.

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“…Here, we presented a safe and effective NKM therapy for potential cancer adjuvant treatment and cancer prevention. We characterized the composition of our NKM cells and investigated the cytotoxicity in vitro and in vivo, and the results showed that they were signi cantly cytotoxic to K562 cells or hepatocellular carcinoma cells [36]. Although NKM therapy may not be as e cient as pure NK therapy, due to its ease of operation and safety (less immune-related side effects were found), we believed that NKM therapy is a su cient treatment for cancer adjuvant therapy, especially in combination with surgery to improve the immune response and eliminate residual cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Immune Normalization Strategy Against Suboptimal Health Status: Safe and Effective Mixed-Natural Killer Cell Therapy

Xing

et al. 2020

Preprint

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Background: Immune normalization has emerged as a new paradigm in immunotherapy, which is proposed in cancer patients instead of the traditional immune enhancement therapy. The immune normalization strategy may also be implemented in cancer prevention of sub-healthy individuals.Methods: We established in vitro cultured mixed-Natural Killer cells (NKM), which could be used to achieve immune normalization. We defined the sub-healthy individuals after analyzing the PD-1 ratio in PBMCs from 95 donors over 50 years of age.Results: NKM were composed by approximately 20% NK cells (CD3-CD16+ or CD56+), 30% NKT-like cells (CD3+CD16+ or CD56+) and other T cells. The in vitro cytotoxicity of NKM was ten times higher than the peripheral blood mononuclear cells (PBMC). NKM cytotoxicity was negatively correlated with the ratio of regulatory T cells (CD3+CD4+ T), and positively correlated with the ratio of NK cells, especially CD56brightCD16bright NK cells. We found the sub-healthy individuals displayed significantly higher ratio of CD3+PD-1+ T cells in PBMC (Ratio > 4%) and higher ratio of CD3+CD8+PD-1+ T cells in CD3+CD8+ T cells (Ratio > 10%) than the healthy controls. Then, we evaluated the potential clinical application of NKM therapy in one pancreatic cancer patient and four sub-healthy individuals.Conclusions: NKM therapy showed good tolerance and no side effects were found. In sub-healthy individuals, the ratio of CD3+PD-1+ T cells and CD3+CD8+PD-1+ T cells was significantly reduced after NKM treatment, which indicated that NKM therapy could potentially be used for cancer prevention and health care, thereby achieving the immune normalization.Trial registration: International Research Center for Regenerative Medicine, BIH-2018-1001. 01 August 2018, BOAO International Hospital.International Research Center for Regenerative Medicine, BIH-2018-1002. 01 August 2018, BOAO International Hospital.

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Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

Cited by 29 publications

References 35 publications

PGLYRP2 as a novel biomarker for the activity and lipid metabolism of systemic lupus erythematosus

PGLYRP2 as a novel biomarker for the activity and lipid metabolism of systemic lupus erythematosus

SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism

Immune Normalization Strategy Against Suboptimal Health Status: Safe and Effective Mixed-Natural Killer Cell Therapy

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