scholarly journals Developments and emerging trends in PD-L1 research in gastrointestinal cancers (2000-2018): a bibliometric perspective

2019 ◽  
Author(s):  
Guangyi Jiang ◽  
Xinjie Zhang ◽  
Hui Liu ◽  
Xingyu Lv ◽  
Fangqiang Wei ◽  
...  
Keyword(s):  
T Cell ◽  
Hot Spot ◽  
Predictive Biomarkers ◽  
Citation Network ◽  
Cell Receptor ◽  
Research Area ◽  
Gastrointestinal Cancers ◽  
Emerging Trends ◽  
Key Concepts ◽  
Author Keywords

Abstract Background: The programmed death-ligand 1 (PD-L1) pathway inhibits T-cell receptor-mediated production of IL-2 and T-cell proliferation and plays an important role in the immunosuppression of various types of cancers. An increasing number of studies have focused on the potential utilization of anti-PD-L1 therapy in gastrointestinal cancers. In this study, we aimed to analyze developments and emerging trends in studies of PD-L1 in gastrointestinal cancers from a bibliometric perspective. Methods: Manuscripts were retrieved from th Web of Science Core Collection (WOSCC) Database. CiteSpace, a bibliometric software, was used to identify landmark studies, key concepts, and various subtopics in this research area. Results: A total of 1325 manuscripts examining PD-L1 in gastrointestinal cancers were included. Manuscripts published in 2017 and 2018 accounted for almost half of the publications (44.2%, 586/1325). Combined with 31,960 references, the manuscripts on this topic constituted a complex co-citation network, and landmark papers were identified by indexes including citation in the network, betweenness centrality, and burstiness . Key concepts such as “Regulatory T cell,” “TIL,” and “Her2” were identified in the co-citation network for author keywords. Furthermore, several subtopics were identified during the process of “clustering” in colorectal, gastroesophageal, and hepatopancreatobiliary cancers, such as “predictive biomarkers”, “advanced cancers”, and “clinical efficacy”. Conclusions: Research on PD-L1 i n gastrointestinal cancers is a rapidly progressing area. More scientific findings are expected in the near future. Analysis and summarization from a bibliometric perspective not onlyidentify landmark manuscripts and hot-spot concepts but also indicate possible directions for future studies.

scholarly journals Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors

2021 ◽  
Vol 12 ◽  
Author(s):  
Laurie G. Landry ◽  
Amanda M. Anderson ◽  
Holger A. Russ ◽  
Liping Yu ◽  
Sally C. Kent ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Cd4 T Cells ◽  
Pancreatic Beta Cells ◽  
Hot Spot ◽  
Cell Receptor ◽  
Organ Donors ◽  
Hla Dq

Proinsulin is an abundant protein that is selectively expressed by pancreatic beta cells and has been a focus for development of antigen-specific immunotherapies for type 1 diabetes (T1D). In this study, we sought to comprehensively evaluate reactivity to preproinsulin by CD4 T cells originally isolated from pancreatic islets of organ donors having T1D. We analyzed 187 T cell receptor (TCR) clonotypes expressed by CD4 T cells obtained from six T1D donors and determined their response to 99 truncated preproinsulin peptide pools, in the presence of autologous B cells. We identified 14 TCR clonotypes from four out of the six donors that responded to preproinsulin peptides. Epitopes were found across all of proinsulin (insulin B-chain, C-peptide, and A-chain) including four hot spot regions containing peptides commonly targeted by TCR clonotypes derived from multiple T1D donors. Of importance, these hot spots overlap with peptide regions to which CD4 T cell responses have previously been detected in the peripheral blood of T1D patients. The 14 TCR clonotypes recognized proinsulin peptides presented by various HLA class II molecules, but there was a trend for dominant restriction with HLA-DQ, especially T1D risk alleles DQ8, DQ2, and DQ8-trans. The characteristics of the tri-molecular complex including proinsulin peptide, HLA-DQ molecule, and TCR derived from CD4 T cells in islets, provides an essential basis for developing antigen-specific biomarkers as well as immunotherapies.

scholarly journals An allosteric hot spot in the tandem-SH2 domain of ZAP-70 regulates T-cell signaling

2020 ◽  
Vol 477 (7) ◽  
pp. 1287-1308 ◽  
Author(s):  
Kaustav Gangopadhyay ◽  
Bharat Manna ◽  
Swarnendu Roy ◽  
Sunitha Kumari ◽  
Olivia Debnath ◽  
...  
Keyword(s):  
T Cell ◽  
Noncovalent Interactions ◽  
Hot Spot ◽  
Cell Receptor ◽  
Kinase Domain ◽  
Sh2 Domain ◽  
T Cell Signaling ◽  
Tcr Signaling ◽  
Sh2 Domains ◽  
Encounter Complex

T-cell receptor (TCR) signaling is initiated by recruiting ZAP-70 to the cytosolic part of TCR. ZAP-70, a non-receptor tyrosine kinase, is composed of an N-terminal tandem SH2 (tSH2) domain connected to the C-terminal kinase domain. The ZAP-70 is recruited to the membrane through binding of tSH2 domain and the doubly phosphorylated ITAM motifs of CD3 chains in the TCR complex. Our results show that the tSH2 domain undergoes a biphasic structural transition while binding to the doubly phosphorylated ITAM-ζ1 peptide. The C-terminal SH2 domain binds first to the phosphotyrosine residue of ITAM peptide to form an encounter complex leading to subsequent binding of second phosphotyrosine residue to the N-SH2 domain. We decipher a network of noncovalent interactions that allosterically couple the two SH2 domains during binding to doubly phosphorylated ITAMs. Mutation in the allosteric network residues, for example, W165C, uncouples the formation of encounter complex to the subsequent ITAM binding thus explaining the altered recruitment of ZAP-70 to the plasma membrane causing autoimmune arthritis in mice. The proposed mechanism of allosteric coupling is unique to ZAP-70, which is fundamentally different from Syk, a close homolog of ZAP-70 expressed in B-cells.

scholarly journals BIBLIOMETRIC ANALYSIS OF WASTE MANAGEMENT AND RECYCLING IN TOURISM SCIENCE FROM PAST TO TODAY

2020 ◽  
pp. 220-236
Author(s):  
Tancel Tercan ◽  
Gauhar Ilyasovna Eshenkulova
Keyword(s):  
Social Network ◽  
Waste Management ◽  
Web Of Science ◽  
Citation Network ◽  
Research Area ◽  
Management Research ◽  
Green Hotel ◽  
Author Keywords ◽  
Number Of Publications ◽  
The Web

The main purpose of study is to examine the researches published in the field of waste management and recycling in tourism science at the period of 1980–2019 with bibliometric perspective and to determine the waste management research area trends in this discipline in the last 39 years. In this context, the Web of Science database was searched under the title of waste management and recycling within the scope of ‘hospitality, leisure and tourism’. In the research, number of publications, publication languages, types of publications, journal co-citation network, author co-citation network, document co-citation network and co-occurring author keywords were analyzed. Social network analysis was used to test purposes. According to the results, it can be said that interest in the field in the context of waste management in tourism publications has increased significantly since 2018. Studies are mainly articles. According to the results, it can be said that Gosling is a pioneer in both waste management and recycling in tourism science. If found that the most commonly used keywords in waste management are sustainability, tourism and food waste. It is determined that the most used words in the field of recycling are tourism, heritage and green hotel.

Trends and Patterns in Turnaround Strategies

2022 ◽  
Vol 14 (1) ◽  
pp. 0-0
Keyword(s):  
Financial Distress ◽  
Corporate Strategy ◽  
Research Area ◽  
Organizational Decline ◽  
Management Journal ◽  
Key Concepts ◽  
Turnaround Strategies ◽  
Author Keywords ◽  
Scopus Database ◽  
Corporate Distress

The paper aims to examine the publications on turnaround strategies and identify scientific gaps. Hence, bibliographic couplings of countries, institutions, journals, publications, authors, and co-occurrences of the author keywords were analyzed. Bibliographic methods were employed to examine and visualize the characteristics of the publications with the aid of VOSViewer software. Using 174 articles from the Scopus database, the results revealed that corporate distress, turnaround, organizational decline, turnaround strategies, corporate strategy, financial distress, retrenchment, turnaround strategy, and turnarounds were among the most studied key concepts in this area, The “Journal of Strategy and Management” and “European Management Journal” were the top journals. United States, United Kingdom, and India were the most influential countries. The Fort Hays University and McMurry University were top research institutions. Notably, Huang, Y., Reddy, K.S., and Xie, E. were the most influential authors in this research area. These results will help academicians and practitioners.

scholarly journals A Mutational Analysis of the Binding of Staphylococcal Enterotoxins B and C3 to the T Cell Receptor β Chain and Major Histocompatibility Complex Class II

1998 ◽  
Vol 187 (6) ◽  
pp. 823-833 ◽  
Author(s):  
Lukas Leder ◽  
Andrea Llera ◽  
Pascal M. Lavoie ◽  
Marina I. Lebedeva ◽  
Hongmin Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Hot Spot ◽  
Cell Receptor ◽  
Class Ii ◽  
Staphylococcal Enterotoxin ◽  
Sedimentation Equilibrium ◽  
Simple Relationship ◽  
Β Chain

The three-dimensional structure of the complex between a T cell receptor (TCR) β chain (mouse Vβ8.2Jβ2.1Cβ1) and the superantigen (SAG) staphylococcal enterotoxin C3 (SEC3) has been recently determined to 3.5 Å resolution. To evaluate the actual contribution of individual SAG residues to stabilizing the β–SEC3 complex, as well as to investigate the relationship between the affinity of SAGs for TCR and MHC and their ability to activate T cells, we measured the binding of a set of SEC3 and staphylococcal enterotoxin B (SEB) mutants to soluble recombinant TCR β chain and to the human MHC class II molecule HLA-DR1. Affinities were determined by sedimentation equilibrium and/or surface plasmon detection, while mitogenic potency was assessed using T cells from rearrangement-deficient TCR transgenic mice. We show that there is a clear and simple relationship between the affinity of SAGs for the TCR and their biological activity: the tighter the binding of a particular mutant of SEC3 or SEB to the TCR β chain, the greater its ability to stimulate T cells. We also find that there is an interplay between TCR–SAG and SAG–MHC interactions in determining mitogenic potency, such that a small increase in the affinity of a SAG for MHC can overcome a large decrease in the SAG's affinity for the TCR. Finally, we observe that those SEC3 residues that make the greatest energetic contribution to stabilizing the β–SEC3 complex (“hot spot” residues) are strictly conserved among enterotoxins reactive with mouse Vβ8.2, thereby providing a basis for understanding why SAGs having other residues at these positions show different Vβ-binding specificities.

scholarly journals How an alloreactive T-cell receptor achieves peptide and MHC specificity

2017 ◽  
Vol 114 (24) ◽  
pp. E4792-E4801 ◽  
Author(s):  
Yuan Wang ◽  
Nishant K. Singh ◽  
Timothy T. Spear ◽  
Lance M. Hellman ◽  
Kurt H. Piepenbrink ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Nonstructural Protein ◽  
Hot Spot ◽  
High Specificity ◽  
Cell Receptor ◽  
Central Tolerance ◽  
Histocompatibility Complex ◽  
Underlying Mechanisms ◽  
Alloreactive T Cell

T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2− individual received an HLA-A2+ liver allograft. HCV1406 was subsequently shown to recognize the HCV nonstructural protein 3 (NS3):1406–1415 epitope with high specificity when presented by HLA-A2. We show that NS3/HLA-A2 recognition by the HCV1406 TCR is critically dependent on features unique to both the allo-MHC and the NS3 epitope. We also find cooperativity between structural mimicry and a crucial peptide “hot spot” and demonstrate its role, along with the MHC, in directing the specificity of allorecognition. Our results help explain the paradox of specificity in alloreactive TCRs and have implications for their use in immunotherapy and related efforts to manipulate TCR recognition, as well as alloreactivity in general.

scholarly journals Immunological Hallmarks for Clinical Response to BCG in Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chun Jye Lim ◽  
Phuong Hoang Diem Nguyen ◽  
Martin Wasser ◽  
Pavanish Kumar ◽  
Yun Hua Lee ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Predictive Biomarkers ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
Muscle Invasive ◽  
Anti Tumor Activity

Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumor activity. We observed the temporal changes of peripheral immune subsets including NKT cells, central memory CD4+ T cells, CD8+ T cells and regulatory T cells (Treg) during the course of BCG. Gene expression analysis revealed enriched immune pathways involving in T cell activation and chemotaxis, as well as a more diversified T cell receptor repertoire in post-BCG tissues. Moreover, tissue multiplexed-immunofluorescence (mIF) showed baseline densities of non-Treg and CD8+PD-1+ T cells were predictive of response and better recurrence-free survival after BCG. Remarkably, post-BCG tissues from responders were found to be infiltrated with more active CD8+PD-1- T cells and non-Treg CD4+FOXP3- T cells; but increased exhausted CD8+PD-1+ T cells were found in non-responders. Taken together, we identified predictive biomarkers for response and uncovered the post-treatment expansion of exhausted PD-1+CD8+ T cells as key to BCG resistance, which could potentially be restored by combining with anti-PD-1 immunotherapy.

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