About: Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits

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About: Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits
Creator	Azuma, Miyuki Copland, Alastair Hart, Peter Paul, Mathew Reljic, Rajko Sparrow, Adam Diogo, Gil
Source	PMC
abstract	Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB), and is also used as an immunotherapy for bladder cancer and other malignancies due to its immunostimulatory properties. Mycobacteria spp., however, are well known for their numerous immune evasion mechanisms that limit the true potential of their therapeutic use. One such major mechanism is the induction of programmed death ligand-1 (PD-L1), which mitigates adaptive immune responses. Here, we sought to unravel the molecular pathways behind PD-L1 up-regulation on antigen-presenting cells (APCs) by BCG. We found that infection of APCs with BCG induced PD-L1 up-regulation, but that this did not depend on direct infection, suggesting a soluble mediator for this effect. BCG induced potent quantities of IL-6 and IL-10, and the downstream transcription factor STAT3 was hyper-phosphorylated. Intracellular analyses revealed that levels of PD-L1 molecules were associated with the STAT3 phosphorylation state, suggesting a causal link. Neutralisation of the IL-6 or IL-10 cytokine receptors dampened STAT3 phosphorylation and BCG-mediated up-regulation of PD-L1 on APCs. Pharmacological inhibition of STAT3 achieved the same effect, confirming an autocrine-paracrine cytokine loop as a mechanism for BCG-mediated up-regulation of PD-L1. Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. These novel findings could lead to refinement of BCG as both a vaccine for infectious disease and as a cancer immunotherapy.
has issue date	2019-03-06(xsd:dateTime)
bibo:doi	10.1038/s41598-019-40145-0
bibo:pmid	30842561
has license	cc-by
sha1sum (hex)	e545cfc731b5511fe89ef69e6d09cbc9bf428704
schema:url	https://doi.org/10.1038/s41598-019-40145-0
resource representing a document's title	Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits
has PubMed Central identifier	PMC6403281
has PubMed identifier	30842561
schema:publication	Sci Rep
resource representing a document's body	covid:e545cfc731b5511fe89ef69e6d09cbc9bf428704#body_text
is schema:about of	named entity 'ANTIGEN' named entity 'cancer immunotherapy' named entity 'blockade' named entity 'mechanisms' named entity 'numerous' named entity 'STAT3' named entity 'Presenting' named entity 'EFFECT' named entity 'CYTOKINE ' named entity 'TRANSCRIPTION FACTOR' named entity 'LIMIT' named entity 'ASSOCIATED WITH' named entity 'PHOSPHORYLATION' named entity 'HERE' named entity 'MOLECULAR PATHWAYS' named entity 'MECHANISMS' named entity 'CONFIRMING' named entity 'AUTOCRINE' named entity 'APCS' named entity 'CYTOKINE RECEPTORS' named entity 'KNOWN' named entity 'TRUE' named entity 'PARACRINE' named entity 'DEPEND' named entity 'FOUND' named entity 'LEVELS' named entity 'DEATH' covid:arg/e545cfc731b5511fe89ef69e6d09cbc9bf428704 named entity 'INDUCTION' named entity 'PROPERTIES' named entity 'PD-L1' named entity 'INFECTION' named entity 'MODEL' named entity 'INTERLEUKIN' named entity 'OPEN' named entity 'BLOCKADE' named entity 'SPP' named entity 'ADAPTIVE IMMUNE RESPONSES' named entity 'BCG' named entity 'CELLS' named entity 'PARACRINE' named entity 'BACILLUS' named entity 'STAT3' named entity 'PD-L1' named entity 'CANCER IMMUNOTHERAPY' named entity 'REVEALED' named entity 'ANTIGEN-PRESENTING CELLS' named entity 'INFECTIOUS DISEASE' named entity 'DID' named entity 'ANTIGEN' named entity 'DIRECT INFECTION' named entity 'NUMEROUS' named entity 'BCG VACCINATION' named entity 'MITIGATES' named entity 'NOVEL' named entity 'BUT' named entity 'BLADDER CANCER' named entity 'MAJOR' named entity 'MECHANISM' named entity 'SPECIFIC' named entity 'IL-10' named entity 'USED' named entity 'THESE' named entity 'STATE' named entity 'MEMORY' named entity 'LOOP' named entity 'INHIBITION' named entity 'IMMUNOTHERAPY' named entity 'INDUCED' named entity 'IN VIVO' named entity 'MEDIATOR' named entity 'UP-REGULATION' named entity 'THERAPEUTIC USE' named entity 'MEDIATED' named entity 'THEIR'

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