Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw
- Autores
- Chiarella, Paula; Vermeulen, Elba Monica; Montagna, Daniela Romina; Vallecorsa, Pablo Daniel; Strazza, Ariel Ramiro; Meiss, Roberto P.; Bustuoabad, Oscar David; Ruggiero, Raul Alejandro; Prehn, Richmond T.
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors), counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth.
Fil: Chiarella, Paula. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Vermeulen, Mónica. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Montagna, Daniela R.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Vallecorsa, Pablo. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Strazza, Ariel Ramiro. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Bustuoabad, Oscar D.. Retired; Argentina
Fil: Ruggiero, Raúl A.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Prehn, Richmond T.. University Of Washington, Seattle; - Materia
-
ANTITUMOR VACCINES
IMMUNE-CHECKPOINTS INHIBITORS
IMMUNOSURVEILLANCE
MURINE TUMORS
TUMOR-IMMUNOSTIMULATION - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/95994
Ver los metadatos del registro completo
id |
CONICETDig_35636349e28ec3717c22f77c70d321dc |
---|---|
oai_identifier_str |
oai:ri.conicet.gov.ar:11336/95994 |
network_acronym_str |
CONICETDig |
repository_id_str |
3498 |
network_name_str |
CONICET Digital (CONICET) |
spelling |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationwChiarella, PaulaVermeulen, Elba MonicaMontagna, Daniela RominaVallecorsa, Pablo DanielStrazza, Ariel RamiroMeiss, Roberto P.Bustuoabad, Oscar DavidRuggiero, Raul AlejandroPrehn, Richmond T.ANTITUMOR VACCINESIMMUNE-CHECKPOINTS INHIBITORSIMMUNOSURVEILLANCEMURINE TUMORSTUMOR-IMMUNOSTIMULATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors), counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth.Fil: Chiarella, Paula. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Vermeulen, Mónica. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Montagna, Daniela R.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Vallecorsa, Pablo. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Strazza, Ariel Ramiro. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Bustuoabad, Oscar D.. Retired; ArgentinaFil: Ruggiero, Raúl A.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Prehn, Richmond T.. University Of Washington, Seattle;Frontiers Media S.A.2018-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95994Chiarella, Paula; Vermeulen, Elba Monica; Montagna, Daniela Romina; Vallecorsa, Pablo Daniel; Strazza, Ariel Ramiro; et al.; Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw; Frontiers Media S.A.; Frontiers in Oncology; 8; 1-2018; 1-132234-943XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fonc.2018.00006/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2018.00006info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:28:23Zoai:ri.conicet.gov.ar:11336/95994instacron: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 10:28:23.687CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw |
title |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw |
spellingShingle |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw Chiarella, Paula ANTITUMOR VACCINES IMMUNE-CHECKPOINTS INHIBITORS IMMUNOSURVEILLANCE MURINE TUMORS TUMOR-IMMUNOSTIMULATION |
title_short |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw |
title_full |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw |
title_fullStr |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw |
title_full_unstemmed |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw |
title_sort |
Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw |
dc.creator.none.fl_str_mv |
Chiarella, Paula Vermeulen, Elba Monica Montagna, Daniela Romina Vallecorsa, Pablo Daniel Strazza, Ariel Ramiro Meiss, Roberto P. Bustuoabad, Oscar David Ruggiero, Raul Alejandro Prehn, Richmond T. |
author |
Chiarella, Paula |
author_facet |
Chiarella, Paula Vermeulen, Elba Monica Montagna, Daniela Romina Vallecorsa, Pablo Daniel Strazza, Ariel Ramiro Meiss, Roberto P. Bustuoabad, Oscar David Ruggiero, Raul Alejandro Prehn, Richmond T. |
author_role |
author |
author2 |
Vermeulen, Elba Monica Montagna, Daniela Romina Vallecorsa, Pablo Daniel Strazza, Ariel Ramiro Meiss, Roberto P. Bustuoabad, Oscar David Ruggiero, Raul Alejandro Prehn, Richmond T. |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
ANTITUMOR VACCINES IMMUNE-CHECKPOINTS INHIBITORS IMMUNOSURVEILLANCE MURINE TUMORS TUMOR-IMMUNOSTIMULATION |
topic |
ANTITUMOR VACCINES IMMUNE-CHECKPOINTS INHIBITORS IMMUNOSURVEILLANCE MURINE TUMORS TUMOR-IMMUNOSTIMULATION |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors), counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth. Fil: Chiarella, Paula. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Vermeulen, Mónica. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Montagna, Daniela R.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Vallecorsa, Pablo. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Strazza, Ariel Ramiro. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Bustuoabad, Oscar D.. Retired; Argentina Fil: Ruggiero, Raúl A.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Prehn, Richmond T.. University Of Washington, Seattle; |
description |
Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors), counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-01 |
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/11336/95994 Chiarella, Paula; Vermeulen, Elba Monica; Montagna, Daniela Romina; Vallecorsa, Pablo Daniel; Strazza, Ariel Ramiro; et al.; Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw; Frontiers Media S.A.; Frontiers in Oncology; 8; 1-2018; 1-13 2234-943X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/95994 |
identifier_str_mv |
Chiarella, Paula; Vermeulen, Elba Monica; Montagna, Daniela Romina; Vallecorsa, Pablo Daniel; Strazza, Ariel Ramiro; et al.; Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw; Frontiers Media S.A.; Frontiers in Oncology; 8; 1-2018; 1-13 2234-943X CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fonc.2018.00006/full info:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2018.00006 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
publisher.none.fl_str_mv |
Frontiers Media S.A. |
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 |
_version_ |
1844614287848374272 |
score |
13.070432 |