What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progressio...

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Autores principales:	Andrea Palicelli, Stefania Croci, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Magda Zanelli, Alcides Chaux, Sofia Cañete-Portillo, Maria Paola Bonasoni, Alessandra Soriano, Stefano Ascani, Maurizio Zizzo, Carolina Castro Ruiz, Antonio De Leo, Guido Giordano, Matteo Landriscina, Giuseppe Carrieri, Luigi Cormio, Daniel M. Berney, Jatin Gandhi, Valerio Copelli, Giuditta Bernardelli, Giacomo Santandrea, Martina Bonacini
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PD-L1 prostate cancer signaling pathways tumor microenvironment target-therapy Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d2e1d8e6f7c7497d859b967c7d899d94
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spelling	oai:doaj.org-article:d2e1d8e6f7c7497d859b967c7d899d942021-11-25T17:55:26ZWhat Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment10.3390/ijms2222123301422-00671661-6596https://doaj.org/article/d2e1d8e6f7c7497d859b967c7d899d942021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12330https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.Andrea PalicelliStefania CrociAlessandra BisagniEleonora ZanettiDario De BiaseBeatrice MelliFrancesca SanguedolceMoira RagazziMagda ZanelliAlcides ChauxSofia Cañete-PortilloMaria Paola BonasoniAlessandra SorianoStefano AscaniMaurizio ZizzoCarolina Castro RuizAntonio De LeoGuido GiordanoMatteo LandriscinaGiuseppe CarrieriLuigi CormioDaniel M. BerneyJatin GandhiValerio CopelliGiuditta BernardelliGiacomo SantandreaMartina BonaciniMDPI AGarticlePD-L1prostatecancersignaling pathwaystumor microenvironmenttarget-therapyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12330, p 12330 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PD-L1 prostate cancer signaling pathways tumor microenvironment target-therapy Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	PD-L1 prostate cancer signaling pathways tumor microenvironment target-therapy Biology (General) QH301-705.5 Chemistry QD1-999 Andrea Palicelli Stefania Croci Alessandra Bisagni Eleonora Zanetti Dario De Biase Beatrice Melli Francesca Sanguedolce Moira Ragazzi Magda Zanelli Alcides Chaux Sofia Cañete-Portillo Maria Paola Bonasoni Alessandra Soriano Stefano Ascani Maurizio Zizzo Carolina Castro Ruiz Antonio De Leo Guido Giordano Matteo Landriscina Giuseppe Carrieri Luigi Cormio Daniel M. Berney Jatin Gandhi Valerio Copelli Giuditta Bernardelli Giacomo Santandrea Martina Bonacini What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment
description	The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.
format	article
author	Andrea Palicelli Stefania Croci Alessandra Bisagni Eleonora Zanetti Dario De Biase Beatrice Melli Francesca Sanguedolce Moira Ragazzi Magda Zanelli Alcides Chaux Sofia Cañete-Portillo Maria Paola Bonasoni Alessandra Soriano Stefano Ascani Maurizio Zizzo Carolina Castro Ruiz Antonio De Leo Guido Giordano Matteo Landriscina Giuseppe Carrieri Luigi Cormio Daniel M. Berney Jatin Gandhi Valerio Copelli Giuditta Bernardelli Giacomo Santandrea Martina Bonacini
author_facet	Andrea Palicelli Stefania Croci Alessandra Bisagni Eleonora Zanetti Dario De Biase Beatrice Melli Francesca Sanguedolce Moira Ragazzi Magda Zanelli Alcides Chaux Sofia Cañete-Portillo Maria Paola Bonasoni Alessandra Soriano Stefano Ascani Maurizio Zizzo Carolina Castro Ruiz Antonio De Leo Guido Giordano Matteo Landriscina Giuseppe Carrieri Luigi Cormio Daniel M. Berney Jatin Gandhi Valerio Copelli Giuditta Bernardelli Giacomo Santandrea Martina Bonacini
author_sort	Andrea Palicelli
title	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment
title_short	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment
title_full	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment
title_fullStr	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment
title_full_unstemmed	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment
title_sort	what do we have to know about pd-l1 expression in prostate cancer? a systematic literature review. part 3: pd-l1, intracellular signaling pathways and tumor microenvironment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d2e1d8e6f7c7497d859b967c7d899d94
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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

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