scholarly journals PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingxia Deng ◽  
Long Peng ◽  
Jiamin Li ◽  
Xiong Liu ◽  
Xichun Xia ◽  
...  
Keyword(s):  
Survival Rates ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Myeloid Derived Suppressor Cell ◽  
Tumor Tissues ◽  
Tumor Types ◽  
The Relationship ◽  
Pan Cancer

Recent studies have shown that PPP1R14B was highly expressed in tumor tissues and patients with high expression of PPP1R14B had poor survival rates. However, the function and mechanisms of PPP1R14B in tumor progression remain ill defined. There was also lack of pan-cancer evidence for the relationship between PPP1R14B and various tumor types based on abundant clinical data. We used the TCGA project and GEO databases to perform pan-cancer analysis of PPP1R14B, including expression differences, correlations between expression levels and survival, genetic alteration, immune infiltration, and relevant cellular pathways, to investigate the functions and potential mechanisms of PPP1R14B in the pathogenesis or clinical prognosis of different cancers. Herein, we found that PPP1R14B was involved in the prognosis of pan-cancer and closely related to immune infiltration. Increased PPP1R14B expression correlated with poor prognosis and increased immune infiltration levels in myeloid-derived suppressor cells (MDSCs). Our studies suggest that PPP1R14B can be used as a prognostic biomarker for pan-cancer. Our findings may provide an antitumor strategy targeting PPP1R14B, including manipulation of tumor cell growth or the tumor microenvironment, especially myeloid-derived suppressor cell infiltration.

scholarly journals Icaritin Induces Anti-tumor Immune Responses in Hepatocellular Carcinoma by Inhibiting Splenic Myeloid-Derived Suppressor Cell Generation

2021 ◽  
Vol 12 ◽  
Author(s):  
Huimin Tao ◽  
Mingyu Liu ◽  
Yuan Wang ◽  
Shufeng Luo ◽  
Yongquan Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Responses ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Extramedullary Hematopoiesis ◽  
Immune Checkpoint Blockade ◽  
Myeloid Derived Suppressor Cell ◽  
Tumor Tissues

Recent studies have demonstrated that splenic extramedullary hematopoiesis (EMH) is an important mechanism for the accumulation of myeloid-derived suppressor cells (MDSCs) in tumor tissues, and thus contributes to disease progression. Icaritin, a prenylflavonoid derivative from plants of the Epimedium genus, has been implicated as a novel immune-modulator that could prolong the survival of hepatocellular carcinoma (HCC) patients. However, it is unclear whether icaritin achieves its anti-tumor effects via the regulation of MDSCs generated by EMH in HCC. Here, we investigated the anti-tumor potential of icaritin and its mechanism of action in murine HCC. Icaritin suppressed tumor progression and significantly prolonged the survival of mice-bearing orthotopic and subcutaneous HCC tumors. Rather than exerting direct cytotoxic activity against tumor cells, icaritin significantly reduced the accumulation and activation of tumoral and splenic MDSCs, and increased the number and activity of cytotoxic T cells. Mechanistically, icaritin downregulates the tumor-associated splenic EMH, thereby reducing the generation and activation of MDSCs. The inhibitory effects of icaritin on human MDSCs in vitro were verified in short-term culture with cord-blood derived hematopoietic precursors. Furthermore, icaritin synergistically enhanced the therapeutic efficacy of immune checkpoint blockade therapy in HCC mice. These findings revealed that icaritin dampens tumoral immunosuppression to elicit anti-tumor immune responses by preventing MDSC generation via the attenuation of EMH. Thus, icaritin may serve as a novel adjuvant or even a stand-alone therapeutic agent for the effective treatment of HCC.

scholarly journals High Expression of PRMT6 Associated With Prognosis and Immune Infiltration in Glioma

2020 ◽  
Author(s):  
Yi Yang ◽  
Zhenshuang Wang ◽  
Shengrong Long ◽  
Jinhai Huang ◽  
Chengran Xu ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Clinical Work ◽  
High Expression ◽  
Clinical Indicators ◽  
Immune Infiltration ◽  
Tumor Tissues ◽  
Potential Biomarker ◽  
Patient Prognosis ◽  
The Relationship

Abstract Background: Gliomas are characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, with the increase of grade, the prognosis of glioma is increasingly poor and not optimistic. Therefore, biological markers for glioma are needed in clinical work, which can be utilized to detect and evaluate the situation and prognosis of glioma patients. Many studies have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors and is associated with patient prognosis. However, the role of PRMT6 in glioma has not been reported or analyzed. Methods: In this study, we used a variety of tumor related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from the perspective of bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. In addition, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from the perspectives of mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results: PRMT6 is significantly differentially expressed in a variety of tumors and is associated with survival and prognosis. Especially in gliomas, the expression of PRMT6 gradually increased with the increase of grade. In addition, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in a variety of databases. Conclusions: Our results indicate that high expression of PRMT6 is a potential biomarker for predicting glioma prognosis and progression.

Analysis of the Myeloid-Derived Suppressor Cells and Annexin A1 in Multibacillary Leprosy and Reactional Episodes

2020 ◽  
Author(s):  
Amilcar Sabino Damazo ◽  
Stephanni Figueiredo da Silva ◽  
Leticia Rossetto da Silva Cavalcante ◽  
Ezequiel Angelo Fonseca Junior ◽  
Joselina Maria da Silva ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Suppressor Cell ◽  
Mycobacterium Leprae ◽  
Histopathological Analysis ◽  
Annexin A1 ◽  
Myeloid Derived Suppressor Cells ◽  
Myeloid Derived Suppressor Cell ◽  
Leprosy Patients ◽  
Multibacillary Leprosy

Abstract Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Patients have distinct clinical forms, and host´s immunological response regulate those manifestations. In this work, the presence of the myeloid-derived suppressor cell and the regulatory protein annexin A1 is described in patients with multibacillary leprosy and with type 1 and 2 reactions. Methods: Patients were submitted to skin biopsy for histopathological analysis to obtain bacilloscopic index. Immunofluorescence was used to detect myeloid-derived suppressor cells and annexin A1.Results: The data demonstrated that the presence of granulocytic and monocytic myeloid-derived suppressor cells in leprosy patients. The high number of monocytic myeloid-derived suppressor cells were observed in lepromatous leprosy and type 2 reactional patients with Bacillus Calmette–Guérin (BCG) vaccination scar. The presence of annexin A1 was observed in all myeloid-derived suppressor cells. In particularly, the monocytic myeloid-derived suppressor cell in the lepromatous patients has higher levels of this protein when compared to the reactional patients. This data suggest that the higher expression of this protein may be related to regulatory response against a severe infection, contributing to anergic response. In type 1 reactional patients, the expression of annexin A1 was reduced. Conclusions: Myeloid-derived suppressor cell are present in leprosy patients and annexin A1 might be regulated the host response against Mycobacterium leprae.

scholarly journals Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
McKenzie K. Hollen ◽  
Julie A. Stortz ◽  
Dijoia Darden ◽  
Marvin L. Dirain ◽  
Dina C. Nacionales ◽  
...  
Keyword(s):  
Cell Function ◽  
Expression Patterns ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
Myeloid Derived Suppressor Cell ◽  
T Lymphocyte Proliferation ◽  
Suppressive Phenotype ◽  
Sepsis Survivors ◽  
Over Time

Abstract Background Sepsis is an increasingly significant challenge throughout the world as one of the major causes of patient morbidity and mortality. Central to the host immunologic response to sepsis is the increase in circulating myeloid-derived suppressor cells (MDSCs), which have been demonstrated to be present and independently associated with poor long-term clinical outcomes. MDSCs are plastic cells and potentially modifiable, particularly through epigenetic interventions. The objective of this study was to determine how the suppressive phenotype of MDSCs evolves after sepsis in surgical ICU patients, as well as to identify epigenetic differences in MDSCs that may explain these changes. Methods Circulating MDSCs from 267 survivors of surgical sepsis were phenotyped at various intervals over 6 weeks, and highly enriched MDSCs from 23 of these samples were co-cultured with CD3/CD28-stimulated autologous T cells. microRNA expression from enriched MDSCs was also identified. Results We observed that MDSC numbers remain significantly elevated in hospitalized sepsis survivors for at least 6 weeks after their infection. However, only MDSCs obtained at and beyond 14 days post-sepsis significantly suppressed T lymphocyte proliferation and IL-2 production. These same MDSCs displayed unique epigenetic (miRNA) expression patterns compared to earlier time points. Conclusions We conclude that in sepsis survivors, immature myeloid cell numbers are increased but the immune suppressive function specific to MDSCs develops over time, and this is associated with a specific epigenome. These findings may explain the chronic and persistent immune suppression seen in these subjects.

Metabolic changes and interaction of tumor cell, myeloid-derived suppressor cell and T cell in hypoxic microenvironment

2020 ◽  
Author(s):  
Xiantu Ou ◽  
Weibiao Lv
Keyword(s):  
Tumor Microenvironment ◽  
Regulatory Protein ◽  
Tumor Hypoxia ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Inflammatory Factors ◽  
Tumor Escape ◽  
Myeloid Derived Suppressor Cells ◽  
Myeloid Derived Suppressor Cell ◽  
Transcriptional Regulatory

It is universally acknowledged that a large number of immune cells, as well as inflammatory factors, regulatory factors and metabolites, accumulate in the tumor microenvironment to jointly promote tumor escape, development and metastasis. Hypoxia is one of the characteristics in tumor microenvironment and is a common phenomenon in all solid tumors. In tumor hypoxia response, there is a key regulator called HIF-1a, which is a key transcriptional regulatory protein that regulates many critical genes. In this paper, the effects of hypoxia on glucose metabolism of tumor cells, myeloid-derived suppressor cells and T cells in tumor microenvironment were reviewed, and the interaction among the three was also described.

scholarly journals Myeloid-derived suppressor cell cytokine secretion as prognostic factor in myelodysplastic syndromes

2020 ◽  
Vol 26 (8) ◽  
pp. 703-715
Author(s):  
Dong Han ◽  
Jinglian Tao ◽  
Rong Fu ◽  
Zonghong Shao
Keyword(s):  
Functional Status ◽  
Myelodysplastic Syndromes ◽  
Poor Prognosis ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Biological Research ◽  
Myeloid Derived Suppressor Cell ◽  
Tnf Α ◽  
Blast Cells ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a critical immunosuppressive role in the tumour micro-environment. Although biological research on MDSCs has made progress, the relationship between the secretion of cytokines by MDSCs and poor prognosis is not clear, and there are no criteria to measure the functional status of MDSCs. Here, we detected the mRNA expression of IL-10, IL-12, TGF-β and TNF-α in MDSCs and the levels of these cytokines in MDSC culture supernatants of patients with myelodysplastic syndromes, and quantified the functional status of MDSCs by IL-10/IL-12 ratio and TGF-β/TNF-α ratio. We found that the ratio of IL-10/IL-12 and TGF-β/TNF-α was significantly higher in higher-risk MDS than in lower-risk MDS and normal control groups. The TGF-β/TNF-α ratio in MDSCs was positively correlated with the percentage of blast cells and was negatively correlated with the percentage of CD3+CD8+ T lymphocytes. Meanwhile, the TGF-β/TNF-α ratio was higher in patients with a lower absolute neutrophil count. It suggested that MDSCs in higher-risk MDS have a stronger immunosuppressive effect and might be related to poor prognosis. Quantifying the functional status of MDSCs with IL-10/IL-12 and TGF-β/TNF-α ratio might help to evaluate the balance of cellular immunity of MDSCs in MDS.

scholarly journals A Novel CD48-Based Analysis of Sepsis-Induced Mouse Myeloid-Derived Suppressor Cell Compartments

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Bei Jia ◽  
Chenchen Zhao ◽  
Guoli Li ◽  
Yaxian Kong ◽  
Yaluan Ma ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Cecal Ligation ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Identification System ◽  
Disease States ◽  
Myeloid Derived Suppressor Cell ◽  
Reporter Mice ◽  
Novel Strategy ◽  
Green Fluorescent

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells that expands dramatically in many disease states and can suppress T-cell responses. MDSCs mainly include monocytic and granulocytic subpopulations that can be distinguished in mice by the expression of Ly6G and Ly6C cell surface markers. This identification system has been validated in experimental tumor models, but not in models of inflammation-associated conditions such as sepsis. We challenged growth factor independent 1 transcription repressor green fluorescent protein (Gfi1:GFP) knock-in reporter mice with cecal ligation and puncture surgery and found that CD11b+Ly6GlowLy6Chigh MDSCs in this sepsis model comprised both monocytic and granulocytic MDSCs. The evidence that conventional Ly6G/Ly6C marker analysis may not be suited to study of inflammation-induced MDSCs led to the development of a novel strategy of distinguishing granulocytic MDSCs from monocytic MDSCs in septic mice by expression of CD48. Application of this novel model should help achieve a more accurate understanding of the inflammation-induced MDSC activity.

scholarly journals Cholangiocarcinoma presents a distinct myeloid-derived suppressor cell signature compared to other hepatobiliary cancers

2019 ◽  
Author(s):  
Defne Bayik ◽  
Adam J. Lauko ◽  
Gustavo A. Roversi ◽  
Emily Serbinowski ◽  
Lou-Anne Acevedo-Moreno ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
The Cancer Genome Atlas ◽  
Limiting Factor ◽  
Isocitrate Dehydrogenase 1 ◽  
Myeloid Derived Suppressor Cell ◽  
Liver Cancers ◽  
Malignant Liver ◽  
Immunosuppressive Cells

AbstractMyeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSC in other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). Investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of the Cancer Genome Atlas demonstrated that a high MDSC score in HCC patients predicted poor disease outcome. Mechanistic studies indicated that the oncometabolite D-2-hydroxyglutarate resulting from isocitrate dehydrogenase 1 mutation could be a limiting factor of MDSC accumulation in CCA patients. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, they may comprise suitable targets for effective immunotherapy approaches.

scholarly journals Immune infiltration of MMP14 in Pan-cancer and its prognostic effect on tumor

2021 ◽  
Author(s):  
Minde Li ◽  
Shaoyang Li ◽  
Lin Zhou ◽  
Le Yang ◽  
Xiao Wu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Mutation Load ◽  
Immune Infiltration ◽  
Tumor Prognosis ◽  
Checkpoint Genes ◽  
The Relationship ◽  
Pan Cancer

Abstract Background: Matrix metallopeptidase 14(MMPL4) is a member of the matrix metalloproteinase family, which interacts with tissue metalloproteinase inhibitors (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 on pan-cancer. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Methods: In this study, we used bioinformatics to analyze data from multiple databases, including TCGA, Oncomine and Kaplan-Meier Plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Results: MMP14 expression is highly associated with prognosis of a variety of cancers, tumor immunoinvasion, and has important effects on pan-oncologic mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes. Conclusion: MMP14 is highly correlated with tumor prognosis and immunoinvasion, and affects the occurrence and progression of many tumors. All these fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis and treatment of many tumors, and provide a new idea and direction for subsequent tumor immune research and treatment strategies.

scholarly journals Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Jia-Nan Cheng ◽  
Yi-Xiao Yuan ◽  
Bo Zhu ◽  
Qingzhu Jia
Keyword(s):  
T Cells ◽  
Tumor Progression ◽  
Therapeutic Response ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Myeloid Derived Suppressor Cell ◽  
Immunosuppressive Tumor Microenvironment ◽  
Immature Myeloid Cells ◽  
Underlying Mechanisms

Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature myeloid cells, has a pivotal role in negatively regulating immune response, promoting tumor progression, creating pre-metastases niche, and weakening immunotherapy efficacy. The underlying mechanisms are complex and diverse, including immunosuppressive functions (such as inhibition of cytotoxic T cells and recruitment of regulatory T cells) and non-immunological functions (mediating stemness and promoting angiogenesis). Moreover, MDSC may predict therapeutic response as a poor prognosis biomarker among multiple tumors. Accumulating evidence indicates targeting MDSC can reverse immunosuppressive tumor microenvironment, and improve therapeutic response either single or combination with immunotherapy. This review summarizes the phenotype and definite mechanisms of MDSCs in tumor progression, and provide new insights of targeting strategies regarding to their clinical applications.

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