What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapy-resistance in PC-patie...

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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, Giacomo Santandrea, Martina Bonacini
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PD-L1 prostate cancer signaling pathways microenvironment target-therapy Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/24141efcf236458cb9f0961939c8a0bd
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spelling	oai:doaj.org-article:24141efcf236458cb9f0961939c8a0bd2021-11-25T17:55:10ZWhat Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)10.3390/ijms2222122971422-00671661-6596https://doaj.org/article/24141efcf236458cb9f0961939c8a0bd2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12297https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ T-cells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and <i>RB</i> deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).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 GandhiGiacomo SantandreaMartina BonaciniMDPI AGarticlePD-L1prostatecancersignaling pathwaysmicroenvironmenttarget-therapyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12297, p 12297 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PD-L1 prostate cancer signaling pathways microenvironment target-therapy Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	PD-L1 prostate cancer signaling pathways 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 Giacomo Santandrea Martina Bonacini What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)
description	In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ T-cells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and <i>RB</i> deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).
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 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 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 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)
title_short	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)
title_full	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)
title_fullStr	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)
title_full_unstemmed	What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)
title_sort	what do we have to know about pd-l1 expression in prostate cancer? a systematic literature review. part 4: experimental treatments in pre-clinical studies (cell lines and mouse models)
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/24141efcf236458cb9f0961939c8a0bd
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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)

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