A commensal symbiotic factor derived fromBacteroides fragilispromotes human CD39+Foxp3+T cells and Tregfunction DOI Open Access
Kiel M. Telesford, Yan Wang, Javier Ochoa‐Repáraz

et al.

Gut Microbes, Journal Year: 2015, Volume and Issue: 6(4), P. 234 - 242

Published: July 4, 2015

Polysaccharide A (PSA) derived from the human commensal Bacteroides fragilis is a symbiosis factor that stimulates immunologic development within mammalian hosts. PSA rebalances skewed systemic T helper responses and promotes regulatory cells (Tregs). However, PSA-mediated induction of Foxp3 in humans has not been reported. In mice, PSA-generated Foxp3+ Tregs dampen Th17 activity thereby facilitating bacterial intestinal colonization while increased presence function these may guard against pathological organ-specific inflammation We herein demonstrate induces expression along with CD39 among naïve CD4 vitro promoting IL-10 secretion. PSA-activated dendritic are essential for mediation this response. When cultured isolated Tregs, enriched expression, enhanced frequency CD39+HLA-DR+ cells, suppressive as measured by decreased TNFα LPS-stimulated monocytes. Our findings first to CD4+Foxp3+ circulating symbiotic factor. Use treatment autoimmune diseases, particular multiple sclerosis inflammatory bowel disease, represent new paradigm approach treating disease.

Language: Английский

Drug resistance and combating drug resistance in cancer DOI Open Access
Xuan Wang, Haiyun Zhang, Xiaozhuo Chen

et al.

Cancer Drug Resistance, Journal Year: 2019, Volume and Issue: unknown

Published: Jan. 1, 2019

Cancer Drug Resistance is an open access journal, focusing on pharmacological aspects of drug resistance and its reversal, molecular mechanisms classes, etc. Both clinical experimental in cancer are included.

Language: Английский

Citations

902
Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors DOI Creative Commons
Thomas Duhen, Rebekka Duhen,

Ryan Montler

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: July 9, 2018

Abstract Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103 + CD39 tumor-infiltrating CD8 (CD8 TIL) are enriched tumor-reactive both in primary metastatic tumors. This TIL subset is found across six different malignancies displays an exhausted tissue-resident memory phenotype. TILs have a distinct T-cell receptor (TCR) repertoire, with clones expanded the but present at low frequencies periphery. also efficiently kill autologous MHC-class I-dependent manner. Finally, higher of head neck associated better overall survival. Our data thus describe approach detecting will help define mechanisms existing treatments, may lead to future adoptive therapies.

Language: Английский

Citations

762
Consensus guidelines for the detection of immunogenic cell death DOI Open Access
Oliver Kepp, Laura Senovilla, Ilio Vitale

et al.

OncoImmunology, Journal Year: 2014, Volume and Issue: 3(9), P. e955691 - e955691

Published: Sept. 2, 2014

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm system, which we named "immunogenic cell death" (ICD). ICD is preceded accompanied emission series immunostimulatory damage-associated molecular patterns (DAMPs) in precise spatiotemporal configuration. Several anticancer agents successfully employed clinic decades, including various chemotherapeutics and radiotherapy, ICD. Moreover, defects components underlie capacity system perceive death immunogenic negatively influence disease outcome among cancer patients treated with inducers. Thus, has profound clinical therapeutic implications. Unfortunately, gold-standard approach detect relies on vaccination experiments involving immunocompetent murine models syngeneic cells, an incompatible large screening campaigns. Here, outline strategies conceived surrogate markers vitro screen chemical libraries putative inducers, based high-content, high-throughput platform recently developed. Such allows detection DAMPs, like surface-exposed calreticulin, extracellular ATP high mobility group box 1 (HMGB1), and/or processes their emission, such endoplasmic reticulum stress, autophagy necrotic plasma membrane permeabilization. We surmise this technology will facilitate development next-generation regimens, kill malignant simultaneously convert them into cancer-specific vaccine.

Language: Английский

Citations

760
The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets DOI
Bertrand Allard, Maria Serena Longhi, Simon C. Robson

et al.

Immunological Reviews, Journal Year: 2017, Volume and Issue: 276(1), P. 121 - 144

Published: March 1, 2017

Summary Cancers are able to grow by subverting immune suppressive pathways, prevent the malignant cells as being recognized dangerous or foreign. This mechanism prevents cancer from eliminated system and allows disease progress a very early stage lethal state. Immunotherapies newly developing interventions that modify patient's fight cancer, either directly stimulating rejection‐type processes blocking pathways. Extracellular adenosine generated ectonucleotidases CD 39 73 is “immune checkpoint mediator” interferes with anti‐tumor responses. In this review, we focus on ectoenzymes encompass aspects of biochemistry these molecules well detailing distribution function cells. Effects inhibition in preclinical clinical studies discussed. Finally, provide insights into potential application adenosinergic other purinergic‐targeting therapies forecast how might develop combination anti‐cancer modalities.

Language: Английский

Citations

758
Targeting immunosuppressive adenosine in cancer DOI

Dipti Vijayan,

Arabella Young, Michele W.L. Teng

et al.

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 17(12), P. 709 - 724

Published: Oct. 23, 2017

Language: Английский

Citations

692
Immunity, inflammation and cancer: a leading role for adenosine DOI
Luca Antonioli, Corrado Blandizzi, Pál Pacher

et al.

Nature reviews. Cancer, Journal Year: 2013, Volume and Issue: 13(12), P. 842 - 857

Published: Nov. 14, 2013

Language: Английский

Citations

675
Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma DOI Creative Commons
David Clark, Saravana M. Dhanasekaran, Francesca Petralia

et al.

Cell, Journal Year: 2019, Volume and Issue: 179(4), P. 964 - 983.e31

Published: Oct. 1, 2019

To elucidate the deregulated functional modules that drive clear cell renal carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration proteogenomic measurements uniquely protein dysregulation cellular mechanisms impacted by alterations, including oxidative phosphorylation-related metabolism, translation processes, phospho-signaling modules. assess degree immune infiltration in individual tumors, microenvironment signatures delineated four immune-based subtypes characterized pathways. This study reports large-scale analysis to discern impact alterations provides evidence for rational treatment selection stemming from pathobiology.

Language: Английский

Citations

583
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption DOI Open Access
Astrid Nehlig

Pharmacological Reviews, Journal Year: 2018, Volume and Issue: 70(2), P. 384 - 411

Published: March 7, 2018

Most individuals adjust their caffeine intake according to the objective and subjective effects induced by methylxanthine. However, reach desired effects, quantity of consumed varies largely among individuals. It has been known for decades that metabolism, clearance, pharmacokinetics is affected many factors such as age, sex hormones, liver disease, obesity, smoking, diet. Caffeine also interacts with medications. All these will be reviewed in present document discussed light most recent data concerning genetic variability affecting levels at pharmacokinetic pharmacodynamic both critically drive level consumption. The are highly variable due a polymorphism CYP1A2 isoform cytochrome P450, which metabolizes 95% ingested. Moreover there another critical enzyme, N-acetyltransferase 2. At level, several polymorphisms main brain target caffeine, adenosine A2A receptor or ADORA2. Genetic studies, including genome-wide association identified loci involved consumption its consequences on sleep, anxiety, potentially neurodegenerative psychiatric diseases. We start reaching better picture how multiplicity biologic mechanisms seems consumption, although much more knowledge still required understand body functions.

Language: Английский

Citations

535
The Coming Decade of Cell Death Research: Five Riddles DOI Creative Commons
Douglas R. Green

Cell, Journal Year: 2019, Volume and Issue: 177(5), P. 1094 - 1107

Published: May 1, 2019

Language: Английский

Citations

473
Classification of current anticancer immunotherapies DOI Open Access
Lorenzo Galluzzi, Erika Vacchelli, José Manuel Bravo‐San Pedro

et al.

Oncotarget, Journal Year: 2014, Volume and Issue: 5(24), P. 12472 - 12508

Published: Dec. 18, 2014

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to robust clinical reality. Many immunotherapeutic regimens are now approved by US Food and Drug Administration European Medicines Agency for use in cancer patients, many others being investigated as standalone interventions or combined with conventional treatments studies. Immunotherapies may be subdivided into "passive" "active" based on their ability engage host immune system against cancer. Since activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies system, this classification does not properly reflect complexity drug-host-tumor interaction. Alternatively, can classified according antigen specificity. While some immunotherapies specifically target one (or few) defined tumor-associated antigen(s), operate relatively non-specific manner boost natural therapy-elicited responses unknown often broad Here, we propose critical, integrated discuss relevance these approaches.

Language: Английский

Citations

444