scholarly journals Identification of Biomarkers for Cervical Cancer Radiotherapy Resistance Based on RNA Sequencing Data

2021 ◽  
Vol 9 ◽  
Author(s):  
Yue Feng ◽  
Zhao Wang ◽  
Nan Yang ◽  
Sijia Liu ◽  
Jiazhuo Yan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Random Forest ◽  
T Cell Activation ◽  
Antigen Processing ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Pearson Correlation ◽  
Functional Enrichment ◽  
Biological Functions ◽  
Radiotherapy Resistance

Cervical cancer as a common gynecological malignancy threatens the health and lives of women. Resistance to radiotherapy is the primary cause of treatment failure and is mainly related to difference in the inherent vulnerability of tumors after radiotherapy. Here, we investigated signature genes associated with poor response to radiotherapy by analyzing an independent cervical cancer dataset from the Gene Expression Omnibus, including pre-irradiation and mid-irradiation information. A total of 316 differentially expressed genes were significantly identified. The correlations between these genes were investigated through the Pearson correlation analysis. Subsequently, random forest model was used in determining cancer-related genes, and all genes were ranked by random forest scoring. The top 30 candidate genes were selected for uncovering their biological functions. Functional enrichment analysis revealed that the biological functions chiefly enriched in tumor immune responses, such as cellular defense response, negative regulation of immune system process, T cell activation, neutrophil activation involved in immune response, regulation of antigen processing and presentation, and peptidyl-tyrosine autophosphorylation. Finally, the top 30 genes were screened and analyzed through literature verification. After validation, 10 genes (KLRK1, LCK, KIF20A, CD247, FASLG, CD163, ZAP70, CD8B, ZNF683, and F10) were to our objective. Overall, the present research confirmed that integrated bioinformatics methods can contribute to the understanding of the molecular mechanisms and potential therapeutic targets underlying radiotherapy resistance in cervical cancer.

scholarly journals NK cell-based cancer immunotherapy: from basic biology to clinical development

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sizhe Liu ◽  
Vasiliy Galat ◽  
Yekaterina Galat4 ◽  
Yoo Kyung Annie Lee ◽  
Derek Wainwright ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
T Cell Activation ◽  
Cell Biology ◽  
Antigen Processing ◽  
Cell Activation ◽  
Nk Cell ◽  
Critical Role ◽  
Clinical Development ◽  
Target Cells ◽  
Immune Effector

AbstractNatural killer (NK) cell is a specialized immune effector cell type that plays a critical role in immune activation against abnormal cells. Different from events required for T cell activation, NK cell activation is governed by the interaction of NK receptors with target cells, independent of antigen processing and presentation. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. In this review, we provide our current understandings of NK cell biology, ongoing pre-clinical and clinical development of NK cell-based therapies and discuss the progress, challenges, and future perspectives.

scholarly journals Immunomodulatory Effects of Polysaccharide from Marine FungusPhoma herbarumYS4108 on T Cells and Dendritic Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Song Chen ◽  
Ran Ding ◽  
Yan Zhou ◽  
Xian Zhang ◽  
Rui Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Interleukin 12 ◽  
Related Factors ◽  
Knock Out ◽  
Specific Immunity

YCP, as a kind of natural polysaccharides from the mycelium of marine filamentous fungusPhoma herbarumYS4108, has great antitumor potentialviaenhancement of host immune response, but little is known about the molecular mechanisms. In the present study, we mainly focused on the effects and mechanisms of YCP on the specific immunity mediated by dendritic cells (DCs) and T cells. T cell /DC activation-related factors including interferon- (IFN-)γ, interleukin-12 (IL-12), and IL-4 were examined with ELISA. Receptor knock-out mice and fluorescence-activated cell sorting are used to analyze the YCP-binding receptor of T cells and DCs. RT-PCR is utilized to measure MAGE-A3 for analyzing the tumor-specific killing effect. In our study, we demonstrated YCP can provide the second signal for T cell activation, proliferation, and IFN-γproduction through binding to toll-like receptor- (TLR-) 2 and TLR-4. YCP could effectively promote IL-12 secretion and expression of markers (CD80, CD86, and MHC II)viaTLR-4 on DCs. Antigen-specific immunity against mouse melanoma cells was strengthened through the activation of T cells and the enhancement of capacity of DCs by YCP. The data supported that YCP can exhibit specific immunomodulatory capacity mediated by T cells and DCs.

scholarly journals Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10800
Author(s):  
Shubhangi Gavali ◽  
Jianing Liu ◽  
Xinyi Li ◽  
Magdalena Paolino
Keyword(s):  
T Cell ◽  
Patient Outcomes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Patient Treatment ◽  
Functional Roles ◽  
Protein Ubiquitination ◽  
Fine Tune

The advent of T-cell-based immunotherapy has remarkably transformed cancer patient treatment. Despite their success, the currently approved immunotherapeutic protocols still encounter limitations, cause toxicity, and give disparate patient outcomes. Thus, a deeper understanding of the molecular mechanisms of T-cell activation and inhibition is much needed to rationally expand targets and possibilities to improve immunotherapies. Protein ubiquitination downstream of immune signaling pathways is essential to fine-tune virtually all immune responses, in particular, the positive and negative regulation of T-cell activation. Numerous studies have demonstrated that deregulation of ubiquitin-dependent pathways can significantly alter T-cell activation and enhance antitumor responses. Consequently, researchers in academia and industry are actively developing technologies to selectively exploit ubiquitin-related enzymes for cancer therapeutics. In this review, we discuss the molecular and functional roles of ubiquitination in key T-cell activation and checkpoint inhibitory pathways to highlight the vast possibilities that targeting ubiquitination offers for advancing T-cell-based immunotherapies.

scholarly journals Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jue Hou ◽  
Shuhui Wang ◽  
Dan Li ◽  
Lindsay N. Carpp ◽  
Tong Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Neutralizing Antibody ◽  
Activator Protein 1 ◽  
Successful Vaccine ◽  
Hiv 1 ◽  
Core Genes

Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced protection from smallpox. We analyzed a subset of samples from a phase 2a trial of three DNA/HIV-1 primes and a recombinant Tiantan vaccinia virus-vectored (rTV)/HIV-1 booster and found that a proportion of participants showed no anti-vaccinia nAb response to the rTV/HIV-1 booster, despite successful vaccine “take.” Using a rich transcriptomic and vaccinia-specific immunological dataset with fine kinetic sampling, we investigated the molecular mechanisms underlying nAb response. Blood transcription module analysis revealed the downregulation of the activator protein 1 (AP-1) pathway in responders, but not in non-responders, and the upregulation of T-cell activation in responders. Furthermore, transcriptional factor network reconstruction revealed the upregulation of AP-1 core genes at hour 4 and day 1 post-rTV/HIV-1 vaccination, followed by a downregulation from day 3 until day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV/HIV-1 vaccination inhibits the nAb response.

scholarly journals Identification of Potential Biomarkers and Related Transcription Factors in Peripheral Blood of Tuberculosis Patients

2020 ◽  
Vol 17 (19) ◽  
pp. 6993
Author(s):  
Longxiang Xie ◽  
Xiaoyu Chao ◽  
Tieshan Teng ◽  
Qiming Li ◽  
Jianping Xie
Keyword(s):  
Transcription Factors ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarkers

Tuberculosis (TB), one major threat to humans, can infect one third of the worldwide population, and cause more than one million deaths each year. This study aimed to identify the effective diagnosis and therapy biomarkers of TB. Hence, we analyzed two microarray datasets (GSE54992 and GSE62525) derived from the Gene Expression Omnibus (GEO) database to find the differentially expressed genes (DEGs) of peripheral blood mononuclear cell (PBMC) between TB patients and healthy specimens. Functional and pathway enrichment of the DEGs were analyzed by Metascape database. Protein-protein interaction (PPI) network among the DEGs were constructed by STRING databases and visualized in Cytoscape software. The related transcription factors regulatory network of the DEGs was also constructed. A total of 190 DEGs including 36 up-regulated genes and 154 down-regulated genes were obtained in TB samples. Gene functional enrichment analysis showed that these DEGs were enriched in T cell activation, chemotaxis, leukocyte activation involved in immune response, cytokine secretion, head development, etc. The top six hub genes (namely, LRRK2, FYN, GART, CCR7, CXCR5, and FASLG) and two significant modules were got from PPI network of DEGs. Vital transcriptional factors, such as FoxC1 and GATA2, were discovered with close interaction with these six hub DEGs. By systemic bioinformatic analysis, many DEGs associated with TB were screened, and these identified hub DEGs may be potential biomarkers for diagnosis and treatment of TB in the future.

scholarly journals Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation

2015 ◽  
Vol 210 (5) ◽  
pp. 851-864 ◽  
Author(s):  
Amanda Carroll-Portillo ◽  
Judy L. Cannon ◽  
Joost te Riet ◽  
Anna Holmes ◽  
Yuko Kawakami ◽  
...  
Keyword(s):  
Immune Response ◽  
Mast Cells ◽  
T Cell Activation ◽  
Antigen Processing ◽  
Cell Activation ◽  
Immunological Synapse ◽  
Specific Antigen ◽  
Cell Interactions ◽  
Dc Function ◽  
Cell Cell

Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation and antigen processing. Whether direct cell–cell interactions are important in modulating MC/DC function is unclear. In this paper, we show that direct contact between MCs and DCs occurs and plays an important role in modulating the immune response. Activation of MCs through FcεRI cross-linking triggers the formation of stable cell–cell interactions with immature DCs that are reminiscent of the immunological synapse. Direct cellular contact differentially regulates the secreted cytokine profile, indicating that MC modulation of DC populations is influenced by the nature of their interaction. Synapse formation requires integrin engagement and facilitates the transfer of internalized MC-specific antigen from MCs to DCs. The transferred material is ultimately processed and presented by DCs and can activate T cells. The physiological outcomes of the MC–DC synapse suggest a new role for intercellular crosstalk in defining the immune response.

Enhanced B7-2 Gene Expression by Interferon-γ in Human Monocytic Cells Is Controlled Through Transcriptional and Posttranscriptional Mechanisms

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1782-1789 ◽  
Author(s):  
R.E. Curiel ◽  
C.S. Garcia ◽  
S. Rottschafer ◽  
M.C. Bosco ◽  
I. Espinoza-Delgado
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Costimulatory Molecule ◽  
Interferon Γ ◽  
Monocytic Cell ◽  
Monocytic Cells ◽  
Enhanced Expression ◽  
Ifn Γ

B7-2 is a costimulatory molecule expressed on professional antigen-presenting cells that provides T cells with a critical signal resulting in T-cell activation. Interferon-γ (IFN-γ) enhances B7-2 protein expression in monocytic cells. However, the molecular mechanisms controlling the enhanced expression of B7-2 are poorly understood. Northern blot and flow cytometry analysis revealed that human monocytes and the human monocytic cell line MonoMac6 (MM6) constitutively expressed B7-2 mRNA and protein and IFN-γ treatment further enhanced the expression of both molecules. The ability of IFN-γ to enhance B7-2 mRNA was evident at the dose of 31 U/mL and reached plateau levels at 500 U/mL. The effects of IFN-γ on B7-2 mRNA expression were time dependent and occurred within 3 hours of treatment and increased through 24 hours. In vitro transcription assays and mRNA stability experiments showed that IFN-γ increases both transcriptional activity and the stability of B7-2 mRNA. Treatment of MM6 cells with cycloheximide showed that de novo protein synthesis was not required for the IFN-γ–enhanced expression of B7-2 mRNA. Overall, these studies show for the first time that IFN-γ–enhanced expression of B7-2 protein in human monocytic cells is controlled at the gene level through a dual mechanism involving transcriptional and posttranscriptional mechanisms.

The antimalarial action of FK506 and rapamycin: evidence for a direct effect on FK506-binding protein PfFKBP35

Parasitology ◽  
2017 ◽  
Vol 144 (7) ◽  
pp. 869-876 ◽  
Author(s):  
PAUL MONAGHAN ◽  
DARREN B. LENEGHAN ◽  
WESLEY SHAW ◽  
ANGUS BELL
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Antimalarial Activity ◽  
Indirect Evidence ◽  
Inhibitory Effect ◽  
Immunosuppressive Drugs ◽  
Fk506 Binding Protein ◽  
Fk506 Binding Proteins ◽  
Antimalarial Action

SUMMARYFK506 and rapamycin (Rap) are immunosuppressive drugs that act principally on T-lymphocytes. The receptors for both drugs are FK506-binding proteins (FKBPs), but the molecular mechanisms of immunosuppression differ. An FK506–FKBP complex inhibits the protein phosphatase calcineurin, blocking a key step in T-cell activation, while the Rap –FKBP complex binds to the protein kinase target of rapamycin (TOR), which is involved in a subsequent signalling pathway. Both drugs, and certain non-immunosuppressive compounds related to FK506, have potent antimalarial activity. There is however conflicting evidence on the involvement of Plasmodium calcineurin in the action of FK506, and the parasite lacks an apparent TOR homologue. We therefore set out to establish whether inhibition of the Plasmodium falciparum FKBP PfFKBP35 itself might be responsible for the antimalarial effects of FK506 and Rap. Similarities in the antiparasitic actions of FK506 and Rap would constitute indirect evidence for this hypothesis. FK506 and Rap acted indistinguishably on: (i) specificity for different intra-erythrocytic stages in culture, (ii) kinetics of killing or irreversible growth arrest of parasites and (iii) interactions with other antimalarial agents. Furthermore, PfFKBP35's inhibitory effect on calcineurin was independent of FK506 under a range of conditions, suggesting that calcineurin is unlikely to be involved in the antimalarial action of FK506.

scholarly journals Identification of an Immune-related Seven-lncRNA Signature Predicting Prognosis and Tumor-infiltrating Immune Cells in Lung Adenocarcinoma

2020 ◽  
Author(s):  
Jinchun Wu ◽  
Yanhua Mou ◽  
Chunfang Zhang ◽  
Chaojun Duan ◽  
Bin Li
Keyword(s):  
Lung Adenocarcinoma ◽  
T Cell Activation ◽  
Immune Cells ◽  
Antigen Processing ◽  
Risk Group ◽  
Pearson Correlation ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Signature ◽  
Immune Pathways

Abstract Background: Lung adenocarcinoma (LUAD) is a common cancer. Immunotherapy is one of the major treatments but showing diverse efficacy in LUAD. Long non-coding RNAs (lncRNAs) are emerging as important players in immune regulation in cancer. Herein, we identified and validated a prognostic signature of immune-related lncRNAs in LUAD and explored its correlation with tumor-infiltrating immune cells (TIICs) by bioinformatics analysis.Methods: Immune-related lncRNAs were acquired using Pearson correlation analysis between lncRNAs from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and immune genes from the ImmPort website and Molecular Signatures Database. The risk signature was constructed in the TCGA group through univariable Cox, lasso and multivariable Cox regression analyses. The prognostic value of the established risk signature was validated in both TCGA and GEO datasets. The interacted TIICs and immune pathways with each single lncRNA and the risk signature were investigated respectively in ImmLnc database, Cibersortx database and gene set enrichment analysis (GSEA) analyses.Results: A seven immune-related lncRNAs prognostic signature was constructed and it stratified LUAD into high and low risk groups. High risk group showed poorer overall survival (OS) in comparison with low risk group via survival analysis.The seven-lncRNAs signature was closely correlated with various TIICs and immune pathways mostly involved in T cell activation, antigen processing and presentation, chemokines and cytokine receptors.Conclusions: The seven lncRNAs model was identified as a predictable signature for prognosis of LUAD patients probably due to its immunomodulation role. This study might provide a new target for enhancing the efficacy of immunotherapy in this mortal disease.

scholarly journals A Monoclonal Antibody to Histoplasma capsulatum Alters the Intracellular Fate of the Fungus in Murine Macrophages

2008 ◽  
Vol 7 (7) ◽  
pp. 1109-1117 ◽  
Author(s):  
Li Shi ◽  
Priscila C. Albuquerque ◽  
Eszter Lazar-Molnar ◽  
Xintao Wang ◽  
Laura Santambrogio ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell Activation ◽  
Antigen Processing ◽  
Cell Activation ◽  
Histoplasma Capsulatum ◽  
Yeast Cells ◽  
Transmission Electron ◽  
Electron And Fluorescence Microscopy ◽  
A Cell ◽  
Intracellular Fate

ABSTRACT Monoclonal antibodies (MAbs) to a cell surface histone on Histoplasma capsulatum modify murine infection and decrease the growth of H. capsulatum within macrophages. Without the MAbs, H. capsulatum survives within macrophages by modifying the intraphagosomal environment. In the present study, we aimed to analyze the affects of a MAb on macrophage phagosomes. Using transmission electron and fluorescence microscopy, we showed that phagosome activation and maturation are significantly greater when H. capsulatum yeast are opsonized with MAb. The MAb reduced the ability of the organism to regulate the phagosomal pH. Additionally, increased antigen processing and reduced negative costimulation occur in macrophages that phagocytose yeast cells opsonized with MAb, resulting in more-efficient T-cell activation. The MAb alters the intracellular fate of H. capsulatum by affecting the ability of the fungus to regulate the milieu of the phagosome.

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