Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro

Autores
Montico, Barbara; Nigro, Annunziata; Lamberti, María Julia; Martorelli, Debora; Mastorci, Katy; Ravo, Maria; Giurato, Giorgio; Steffan, Agostino; Dolcetti, Riccardo; Casolaro, Vincenzo; Dal Col, Jessica
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background aims: Whole tumor cell lysates (TCLs) obtained from cancer cells previously killed by treatments able to promote immunogenic cell death (ICD) can be efficiently used as a source of tumor-associated antigens for the development of highly efficient dendritic cell (DC)-based vaccines. Herein, the potential role of the interferon (IFN)-inducible protein phospholipid scramblase 1 (PLSCR1) in influencing immunogenic features of dying cancer cells and in enhancing DC-based vaccine efficiency was investigated. Methods: PLSCR1 expression was evaluated in different mantle-cell lymphoma (MCL) cell lines following ICD induction by 9-cis-retinoic acid (RA)/IFN-α combination, and commercial kinase inhibitor was used to identify the signaling pathway involved in its upregulation. A Mino cell line ectopically expressing PLSCR1 was generated to investigate the potential involvement of this protein in modulating ICD features. Whole TCLs obtained from Mino overexpressing PLSCR1 were used for DC loading, and loaded DCs were employed for generation of tumor antigen-specific cytotoxic T lymphocytes. Results: The ICD inducer RA/IFN-α combination promoted PLSCR1 expression through STAT1 activation. PLSCR1 upregulation favored pro-apoptotic effects of RA/IFN-α treatment and enhanced the exposure of calreticulin on cell surface. Moreover, DCs loaded with TCLs obtained from Mino ectopically expressing PLSCR1 elicited in vitro greater T-cell–mediated antitumor responses compared with DCs loaded with TCLs derived from Mino infected with empty vector or the parental cell line. Conversely, PLSCR1 knock-down inhibited the stimulating activity of DCs loaded with RA/IFN-α–treated TCLs to elicit cyclin D1 peptide-specific cytotoxic T lymphocytes. Conclusions: Our results indicate that PLSCR1 improved ICD-associated calreticulin exposure induced by RA/IFN-α and was clearly involved in DC-based vaccine efficiency as well, suggesting a potential contribution in the control of pathways associated to DC activation, possibly including those involved in antigen uptake and concomitant antitumor immune response activation.
Fil: Montico, Barbara. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Nigro, Annunziata. Universita di Salerno; Italia
Fil: Lamberti, María Julia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto; Argentina
Fil: Martorelli, Debora. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Mastorci, Katy. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Ravo, Maria. Genomix 4 Life; Italia
Fil: Giurato, Giorgio. Universita di Salerno; Italia
Fil: Steffan, Agostino. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Dolcetti, Riccardo. University of Melbourne; Australia
Fil: Casolaro, Vincenzo. Universita di Salerno; Italia
Fil: Dal Col, Jessica. Universita di Salerno; Italia
Materia
DC-BASED VACCINE
IMMUNOGENIC CELL DEATH
MANTLE CELL LYMPHOMA
PHOSPHOLIPID SCRAMBLASE 1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/227002
Acceder
id CONICETDig_ada2d0932b75778dd069891039911c02
oai_identifier_str oai:ri.conicet.gov.ar:11336/227002
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitroMontico, BarbaraNigro, AnnunziataLamberti, María JuliaMartorelli, DeboraMastorci, KatyRavo, MariaGiurato, GiorgioSteffan, AgostinoDolcetti, RiccardoCasolaro, VincenzoDal Col, JessicaDC-BASED VACCINEIMMUNOGENIC CELL DEATHMANTLE CELL LYMPHOMAPHOSPHOLIPID SCRAMBLASE 1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background aims: Whole tumor cell lysates (TCLs) obtained from cancer cells previously killed by treatments able to promote immunogenic cell death (ICD) can be efficiently used as a source of tumor-associated antigens for the development of highly efficient dendritic cell (DC)-based vaccines. Herein, the potential role of the interferon (IFN)-inducible protein phospholipid scramblase 1 (PLSCR1) in influencing immunogenic features of dying cancer cells and in enhancing DC-based vaccine efficiency was investigated. Methods: PLSCR1 expression was evaluated in different mantle-cell lymphoma (MCL) cell lines following ICD induction by 9-cis-retinoic acid (RA)/IFN-α combination, and commercial kinase inhibitor was used to identify the signaling pathway involved in its upregulation. A Mino cell line ectopically expressing PLSCR1 was generated to investigate the potential involvement of this protein in modulating ICD features. Whole TCLs obtained from Mino overexpressing PLSCR1 were used for DC loading, and loaded DCs were employed for generation of tumor antigen-specific cytotoxic T lymphocytes. Results: The ICD inducer RA/IFN-α combination promoted PLSCR1 expression through STAT1 activation. PLSCR1 upregulation favored pro-apoptotic effects of RA/IFN-α treatment and enhanced the exposure of calreticulin on cell surface. Moreover, DCs loaded with TCLs obtained from Mino ectopically expressing PLSCR1 elicited in vitro greater T-cell–mediated antitumor responses compared with DCs loaded with TCLs derived from Mino infected with empty vector or the parental cell line. Conversely, PLSCR1 knock-down inhibited the stimulating activity of DCs loaded with RA/IFN-α–treated TCLs to elicit cyclin D1 peptide-specific cytotoxic T lymphocytes. Conclusions: Our results indicate that PLSCR1 improved ICD-associated calreticulin exposure induced by RA/IFN-α and was clearly involved in DC-based vaccine efficiency as well, suggesting a potential contribution in the control of pathways associated to DC activation, possibly including those involved in antigen uptake and concomitant antitumor immune response activation.Fil: Montico, Barbara. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; ItaliaFil: Nigro, Annunziata. Universita di Salerno; ItaliaFil: Lamberti, María Julia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto; ArgentinaFil: Martorelli, Debora. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; ItaliaFil: Mastorci, Katy. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; ItaliaFil: Ravo, Maria. Genomix 4 Life; ItaliaFil: Giurato, Giorgio. Universita di Salerno; ItaliaFil: Steffan, Agostino. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; ItaliaFil: Dolcetti, Riccardo. University of Melbourne; AustraliaFil: Casolaro, Vincenzo. Universita di Salerno; ItaliaFil: Dal Col, Jessica. Universita di Salerno; ItaliaTaylor & Francis As2023-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227002Montico, Barbara; Nigro, Annunziata; Lamberti, María Julia; Martorelli, Debora; Mastorci, Katy; et al.; Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro; Taylor & Francis As; Cytotherapy; 26; 2; 12-2023; 145-1561465-3249CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jcyt.2023.11.014info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1465324923011271info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:44:18Zoai:ri.conicet.gov.ar:11336/227002instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:44:18.288CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
title Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
spellingShingle Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
Montico, Barbara
DC-BASED VACCINE
IMMUNOGENIC CELL DEATH
MANTLE CELL LYMPHOMA
PHOSPHOLIPID SCRAMBLASE 1
title_short Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
title_full Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
title_fullStr Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
title_full_unstemmed Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
title_sort Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro
dc.creator.none.fl_str_mv Montico, Barbara
Nigro, Annunziata
Lamberti, María Julia
Martorelli, Debora
Mastorci, Katy
Ravo, Maria
Giurato, Giorgio
Steffan, Agostino
Dolcetti, Riccardo
Casolaro, Vincenzo
Dal Col, Jessica
author Montico, Barbara
author_facet Montico, Barbara
Nigro, Annunziata
Lamberti, María Julia
Martorelli, Debora
Mastorci, Katy
Ravo, Maria
Giurato, Giorgio
Steffan, Agostino
Dolcetti, Riccardo
Casolaro, Vincenzo
Dal Col, Jessica
author_role author
author2 Nigro, Annunziata
Lamberti, María Julia
Martorelli, Debora
Mastorci, Katy
Ravo, Maria
Giurato, Giorgio
Steffan, Agostino
Dolcetti, Riccardo
Casolaro, Vincenzo
Dal Col, Jessica
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DC-BASED VACCINE
IMMUNOGENIC CELL DEATH
MANTLE CELL LYMPHOMA
PHOSPHOLIPID SCRAMBLASE 1
topic DC-BASED VACCINE
IMMUNOGENIC CELL DEATH
MANTLE CELL LYMPHOMA
PHOSPHOLIPID SCRAMBLASE 1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background aims: Whole tumor cell lysates (TCLs) obtained from cancer cells previously killed by treatments able to promote immunogenic cell death (ICD) can be efficiently used as a source of tumor-associated antigens for the development of highly efficient dendritic cell (DC)-based vaccines. Herein, the potential role of the interferon (IFN)-inducible protein phospholipid scramblase 1 (PLSCR1) in influencing immunogenic features of dying cancer cells and in enhancing DC-based vaccine efficiency was investigated. Methods: PLSCR1 expression was evaluated in different mantle-cell lymphoma (MCL) cell lines following ICD induction by 9-cis-retinoic acid (RA)/IFN-α combination, and commercial kinase inhibitor was used to identify the signaling pathway involved in its upregulation. A Mino cell line ectopically expressing PLSCR1 was generated to investigate the potential involvement of this protein in modulating ICD features. Whole TCLs obtained from Mino overexpressing PLSCR1 were used for DC loading, and loaded DCs were employed for generation of tumor antigen-specific cytotoxic T lymphocytes. Results: The ICD inducer RA/IFN-α combination promoted PLSCR1 expression through STAT1 activation. PLSCR1 upregulation favored pro-apoptotic effects of RA/IFN-α treatment and enhanced the exposure of calreticulin on cell surface. Moreover, DCs loaded with TCLs obtained from Mino ectopically expressing PLSCR1 elicited in vitro greater T-cell–mediated antitumor responses compared with DCs loaded with TCLs derived from Mino infected with empty vector or the parental cell line. Conversely, PLSCR1 knock-down inhibited the stimulating activity of DCs loaded with RA/IFN-α–treated TCLs to elicit cyclin D1 peptide-specific cytotoxic T lymphocytes. Conclusions: Our results indicate that PLSCR1 improved ICD-associated calreticulin exposure induced by RA/IFN-α and was clearly involved in DC-based vaccine efficiency as well, suggesting a potential contribution in the control of pathways associated to DC activation, possibly including those involved in antigen uptake and concomitant antitumor immune response activation.
Fil: Montico, Barbara. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Nigro, Annunziata. Universita di Salerno; Italia
Fil: Lamberti, María Julia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto; Argentina
Fil: Martorelli, Debora. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Mastorci, Katy. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Ravo, Maria. Genomix 4 Life; Italia
Fil: Giurato, Giorgio. Universita di Salerno; Italia
Fil: Steffan, Agostino. Centro Di Riferimento Oncologico Di Aviano; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia
Fil: Dolcetti, Riccardo. University of Melbourne; Australia
Fil: Casolaro, Vincenzo. Universita di Salerno; Italia
Fil: Dal Col, Jessica. Universita di Salerno; Italia
description Background aims: Whole tumor cell lysates (TCLs) obtained from cancer cells previously killed by treatments able to promote immunogenic cell death (ICD) can be efficiently used as a source of tumor-associated antigens for the development of highly efficient dendritic cell (DC)-based vaccines. Herein, the potential role of the interferon (IFN)-inducible protein phospholipid scramblase 1 (PLSCR1) in influencing immunogenic features of dying cancer cells and in enhancing DC-based vaccine efficiency was investigated. Methods: PLSCR1 expression was evaluated in different mantle-cell lymphoma (MCL) cell lines following ICD induction by 9-cis-retinoic acid (RA)/IFN-α combination, and commercial kinase inhibitor was used to identify the signaling pathway involved in its upregulation. A Mino cell line ectopically expressing PLSCR1 was generated to investigate the potential involvement of this protein in modulating ICD features. Whole TCLs obtained from Mino overexpressing PLSCR1 were used for DC loading, and loaded DCs were employed for generation of tumor antigen-specific cytotoxic T lymphocytes. Results: The ICD inducer RA/IFN-α combination promoted PLSCR1 expression through STAT1 activation. PLSCR1 upregulation favored pro-apoptotic effects of RA/IFN-α treatment and enhanced the exposure of calreticulin on cell surface. Moreover, DCs loaded with TCLs obtained from Mino ectopically expressing PLSCR1 elicited in vitro greater T-cell–mediated antitumor responses compared with DCs loaded with TCLs derived from Mino infected with empty vector or the parental cell line. Conversely, PLSCR1 knock-down inhibited the stimulating activity of DCs loaded with RA/IFN-α–treated TCLs to elicit cyclin D1 peptide-specific cytotoxic T lymphocytes. Conclusions: Our results indicate that PLSCR1 improved ICD-associated calreticulin exposure induced by RA/IFN-α and was clearly involved in DC-based vaccine efficiency as well, suggesting a potential contribution in the control of pathways associated to DC activation, possibly including those involved in antigen uptake and concomitant antitumor immune response activation.
publishDate 2023
dc.date.none.fl_str_mv 2023-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/227002
Montico, Barbara; Nigro, Annunziata; Lamberti, María Julia; Martorelli, Debora; Mastorci, Katy; et al.; Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro; Taylor & Francis As; Cytotherapy; 26; 2; 12-2023; 145-156
1465-3249
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227002
identifier_str_mv Montico, Barbara; Nigro, Annunziata; Lamberti, María Julia; Martorelli, Debora; Mastorci, Katy; et al.; Phospholipid scramblase 1 is involved in immunogenic cell death and contributes to dendritic cell–based vaccine efficiency to elicit antitumor immune response in vitro; Taylor & Francis As; Cytotherapy; 26; 2; 12-2023; 145-156
1465-3249
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jcyt.2023.11.014
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1465324923011271
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis As
publisher.none.fl_str_mv Taylor & Francis As
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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