Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor

Autores
Montagna, Daniela Romina; Duarte, Alejandra Beatriz; Chiarella, Paula; Rearte, María Bárbara; Bustuoabad, Oscar David; Vermeulen, Elba Monica; Ruggiero, Raul Alejandro
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Although immune-checkpoint inhibitors (ICI) are overall promissory for cancer treatment, they entail, in some cases, an undesired side-effect called hyperprogressive-cancer disease (HPD) associated with acceleration of tumor growth and shortened survival. Methods: To understand the mechanisms of HPD we assayed the ICI therapy on two murine tumors widely different regarding immunogenicity and, subsequently, on models of local recurrences and metastases of these tumors. To potentiate the immune response (IR), we combined ICI with meta-tyrosine—that counteracts immune-suppressive signals—and a selective inhibitor of p38 pathway that proved to counteract the phenomenon of tumor-immunostimulation. Results: ICI were therapeutically effective against both tumor models (proportionally to their immunogenicity) but only when they faced incipient tumors. In contrast, ICI produced acceleration of large and residual tumors. The combined treatment strongly inhibited the growth of large tumors and it managed to cure 80% of mice with local recurrences and 60% of mice bearing residual metastases. Conclusions: Tumor enhancement was paradoxically correlated to a weak increase of the antitumor IR suggesting that a weak IR – different from a strong tumor-inhibitory one—may produce stimulation of tumor growth, mimicking the HPD observed in some clinical settings.
Fil: Montagna, Daniela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Duarte, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
HYPERPROGRESSIVE CANCER DISEASE
IMMUNE CHECKPOINTS INHIBITORS
META-TYROSINE
METASTASES
MURINE TUMORS
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:11336/214901
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/214901
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitorMontagna, Daniela RominaDuarte, Alejandra BeatrizChiarella, PaulaRearte, María BárbaraBustuoabad, Oscar DavidVermeulen, Elba MonicaRuggiero, Raul AlejandroHYPERPROGRESSIVE CANCER DISEASEIMMUNE CHECKPOINTS INHIBITORSMETA-TYROSINEMETASTASESMURINE TUMORShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Although immune-checkpoint inhibitors (ICI) are overall promissory for cancer treatment, they entail, in some cases, an undesired side-effect called hyperprogressive-cancer disease (HPD) associated with acceleration of tumor growth and shortened survival. Methods: To understand the mechanisms of HPD we assayed the ICI therapy on two murine tumors widely different regarding immunogenicity and, subsequently, on models of local recurrences and metastases of these tumors. To potentiate the immune response (IR), we combined ICI with meta-tyrosine—that counteracts immune-suppressive signals—and a selective inhibitor of p38 pathway that proved to counteract the phenomenon of tumor-immunostimulation. Results: ICI were therapeutically effective against both tumor models (proportionally to their immunogenicity) but only when they faced incipient tumors. In contrast, ICI produced acceleration of large and residual tumors. The combined treatment strongly inhibited the growth of large tumors and it managed to cure 80% of mice with local recurrences and 60% of mice bearing residual metastases. Conclusions: Tumor enhancement was paradoxically correlated to a weak increase of the antitumor IR suggesting that a weak IR – different from a strong tumor-inhibitory one—may produce stimulation of tumor growth, mimicking the HPD observed in some clinical settings.Fil: Montagna, Daniela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Duarte, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaBioMed Central2022-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/214901Montagna, Daniela Romina; Duarte, Alejandra Beatriz; Chiarella, Paula; Rearte, María Bárbara; Bustuoabad, Oscar David; et al.; Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor; BioMed Central; BMC Cancer; 22; 1; 3-2022; 1-171471-2407CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09941-2info:eu-repo/semantics/altIdentifier/doi/10.1186/s12885-022-09941-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:15:39Zoai:ri.conicet.gov.ar:11336/214901instacron: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:34982025-10-22 12:15:40.296CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
title Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
spellingShingle Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
Montagna, Daniela Romina
HYPERPROGRESSIVE CANCER DISEASE
IMMUNE CHECKPOINTS INHIBITORS
META-TYROSINE
METASTASES
MURINE TUMORS
title_short Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
title_full Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
title_fullStr Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
title_full_unstemmed Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
title_sort Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
dc.creator.none.fl_str_mv Montagna, Daniela Romina
Duarte, Alejandra Beatriz
Chiarella, Paula
Rearte, María Bárbara
Bustuoabad, Oscar David
Vermeulen, Elba Monica
Ruggiero, Raul Alejandro
author Montagna, Daniela Romina
author_facet Montagna, Daniela Romina
Duarte, Alejandra Beatriz
Chiarella, Paula
Rearte, María Bárbara
Bustuoabad, Oscar David
Vermeulen, Elba Monica
Ruggiero, Raul Alejandro
author_role author
author2 Duarte, Alejandra Beatriz
Chiarella, Paula
Rearte, María Bárbara
Bustuoabad, Oscar David
Vermeulen, Elba Monica
Ruggiero, Raul Alejandro
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HYPERPROGRESSIVE CANCER DISEASE
IMMUNE CHECKPOINTS INHIBITORS
META-TYROSINE
METASTASES
MURINE TUMORS
topic HYPERPROGRESSIVE CANCER DISEASE
IMMUNE CHECKPOINTS INHIBITORS
META-TYROSINE
METASTASES
MURINE TUMORS
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: Although immune-checkpoint inhibitors (ICI) are overall promissory for cancer treatment, they entail, in some cases, an undesired side-effect called hyperprogressive-cancer disease (HPD) associated with acceleration of tumor growth and shortened survival. Methods: To understand the mechanisms of HPD we assayed the ICI therapy on two murine tumors widely different regarding immunogenicity and, subsequently, on models of local recurrences and metastases of these tumors. To potentiate the immune response (IR), we combined ICI with meta-tyrosine—that counteracts immune-suppressive signals—and a selective inhibitor of p38 pathway that proved to counteract the phenomenon of tumor-immunostimulation. Results: ICI were therapeutically effective against both tumor models (proportionally to their immunogenicity) but only when they faced incipient tumors. In contrast, ICI produced acceleration of large and residual tumors. The combined treatment strongly inhibited the growth of large tumors and it managed to cure 80% of mice with local recurrences and 60% of mice bearing residual metastases. Conclusions: Tumor enhancement was paradoxically correlated to a weak increase of the antitumor IR suggesting that a weak IR – different from a strong tumor-inhibitory one—may produce stimulation of tumor growth, mimicking the HPD observed in some clinical settings.
Fil: Montagna, Daniela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Duarte, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Background: Although immune-checkpoint inhibitors (ICI) are overall promissory for cancer treatment, they entail, in some cases, an undesired side-effect called hyperprogressive-cancer disease (HPD) associated with acceleration of tumor growth and shortened survival. Methods: To understand the mechanisms of HPD we assayed the ICI therapy on two murine tumors widely different regarding immunogenicity and, subsequently, on models of local recurrences and metastases of these tumors. To potentiate the immune response (IR), we combined ICI with meta-tyrosine—that counteracts immune-suppressive signals—and a selective inhibitor of p38 pathway that proved to counteract the phenomenon of tumor-immunostimulation. Results: ICI were therapeutically effective against both tumor models (proportionally to their immunogenicity) but only when they faced incipient tumors. In contrast, ICI produced acceleration of large and residual tumors. The combined treatment strongly inhibited the growth of large tumors and it managed to cure 80% of mice with local recurrences and 60% of mice bearing residual metastases. Conclusions: Tumor enhancement was paradoxically correlated to a weak increase of the antitumor IR suggesting that a weak IR – different from a strong tumor-inhibitory one—may produce stimulation of tumor growth, mimicking the HPD observed in some clinical settings.
publishDate 2022
dc.date.none.fl_str_mv 2022-03
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/11336/214901
Montagna, Daniela Romina; Duarte, Alejandra Beatriz; Chiarella, Paula; Rearte, María Bárbara; Bustuoabad, Oscar David; et al.; Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor; BioMed Central; BMC Cancer; 22; 1; 3-2022; 1-17
1471-2407
CONICET Digital
CONICET
url http://hdl.handle.net/11336/214901
identifier_str_mv Montagna, Daniela Romina; Duarte, Alejandra Beatriz; Chiarella, Paula; Rearte, María Bárbara; Bustuoabad, Oscar David; et al.; Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor; BioMed Central; BMC Cancer; 22; 1; 3-2022; 1-17
1471-2407
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09941-2
info:eu-repo/semantics/altIdentifier/doi/10.1186/s12885-022-09941-2
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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 13.229304

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