Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Marzia Pucci, Stefania Raimondo, Ornella Urzì, Marta Moschetti, Maria Antonietta Di Bella, Alice Conigliaro, Nadia Caccamo, Marco Pio La Manna, Simona Fontana, Riccardo Alessandro
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	small extracellular vesicles M0 macrophages PD-L1 TLR4 colorectal cancer multiple myeloma Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/b9ed3f2105a84ff789755d2c3f2aa606
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b9ed3f2105a84ff789755d2c3f2aa606
record_format	dspace
spelling	oai:doaj.org-article:b9ed3f2105a84ff789755d2c3f2aa6062021-11-25T17:53:31ZTumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways10.3390/ijms2222121181422-00671661-6596https://doaj.org/article/b9ed3f2105a84ff789755d2c3f2aa6062021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12118https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.Marzia PucciStefania RaimondoOrnella UrzìMarta MoschettiMaria Antonietta Di BellaAlice ConigliaroNadia CaccamoMarco Pio La MannaSimona FontanaRiccardo AlessandroMDPI AGarticlesmall extracellular vesiclesM0 macrophagesPD-L1TLR4colorectal cancermultiple myelomaBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12118, p 12118 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	small extracellular vesicles M0 macrophages PD-L1 TLR4 colorectal cancer multiple myeloma Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	small extracellular vesicles M0 macrophages PD-L1 TLR4 colorectal cancer multiple myeloma Biology (General) QH301-705.5 Chemistry QD1-999 Marzia Pucci Stefania Raimondo Ornella Urzì Marta Moschetti Maria Antonietta Di Bella Alice Conigliaro Nadia Caccamo Marco Pio La Manna Simona Fontana Riccardo Alessandro Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
description	Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.
format	article
author	Marzia Pucci Stefania Raimondo Ornella Urzì Marta Moschetti Maria Antonietta Di Bella Alice Conigliaro Nadia Caccamo Marco Pio La Manna Simona Fontana Riccardo Alessandro
author_facet	Marzia Pucci Stefania Raimondo Ornella Urzì Marta Moschetti Maria Antonietta Di Bella Alice Conigliaro Nadia Caccamo Marco Pio La Manna Simona Fontana Riccardo Alessandro
author_sort	Marzia Pucci
title	Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
title_short	Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
title_full	Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
title_fullStr	Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
title_full_unstemmed	Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
title_sort	tumor-derived small extracellular vesicles induce pro-inflammatory cytokine expression and pd-l1 regulation in m0 macrophages via il-6/stat3 and tlr4 signaling pathways
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b9ed3f2105a84ff789755d2c3f2aa606
work_keys_str_mv	AT marziapucci tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT stefaniaraimondo tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT ornellaurzi tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT martamoschetti tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT mariaantoniettadibella tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT aliceconigliaro tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT nadiacaccamo tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT marcopiolamanna tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT simonafontana tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways AT riccardoalessandro tumorderivedsmallextracellularvesiclesinduceproinflammatorycytokineexpressionandpdl1regulationinm0macrophagesviail6stat3andtlr4signalingpathways
_version_	1718411883453612032

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways

Ejemplares similares