Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Hardy-Werbin, Max; Rocha, Pedro P.; Arpí Llucià, Oriol; Taus García, Álvaro; Nonell Mazelon, Lara, 1972-; Duran Jordà, Xavier, 1974-; Villanueva, Xavier; Joseph-Pietras, Debora; Nolan, Luke; Danson, Sarah; Griffiths, Richard; López-Botet, M. (Miguel); Rovira Guerín, Ana; Albanell Mestres, Joan; Ottensmeier, Christian; Arriola Aperribay, Edurne

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chem...

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Autores:	Hardy-Werbin, Max, Rocha, Pedro P., Arpí Llucià, Oriol, Taus García, Álvaro, Nonell Mazelon, Lara, 1972-, Duran Jordà, Xavier, 1974-, Villanueva, Xavier, Joseph-Pietras, Debora, Nolan, Luke, Danson, Sarah, Griffiths, Richard, López-Botet, M. (Miguel), Rovira Guerín, Ana, Albanell Mestres, Joan, Ottensmeier, Christian, Arriola Aperribay, Edurne
Tipo de recurso:	artículo
Estado:	Versión aceptada para publicación
Fecha de publicación:	2019
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:10230/44002
Acceso en línea:	http://hdl.handle.net/10230/44002 http://dx.doi.org/10.1080/2162402X.2019.1593810
Access Level:	acceso abierto
Palabra clave:	Biomarkers Cytokines Immunotherapy Ipilimumab Small cell lung cancer

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spelling	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancerHardy-Werbin, MaxRocha, Pedro P.Arpí Llucià, OriolTaus García, ÁlvaroNonell Mazelon, Lara, 1972-Duran Jordà, Xavier, 1974-Villanueva, XavierJoseph-Pietras, DeboraNolan, LukeDanson, SarahGriffiths, RichardLópez-Botet, M. (Miguel)Rovira Guerín, AnaAlbanell Mestres, JoanOttensmeier, ChristianArriola Aperribay, EdurneBiomarkersCytokinesImmunotherapyIpilimumabSmall cell lung cancerBackground. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival. Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated. Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival. Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC.Taylor & Francis20202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44002http://dx.doi.org/10.1080/2162402X.2019.1593810reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésOncoimmunology. 2019;8(6):e1593810© This is an Accepted Manuscript of an article published by Taylor & Francis in Oncoimmunology on 2019, available online: http://www.tandfonline.com/10.1080/2162402X.2019.1593810.info:eu-repo/semantics/openAccessoai:recercat.cat:10230/440022026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
title	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
spellingShingle	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer Hardy-Werbin, Max Biomarkers Cytokines Immunotherapy Ipilimumab Small cell lung cancer
title_short	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
title_full	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
title_fullStr	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
title_full_unstemmed	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
title_sort	Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
dc.creator.none.fl_str_mv	Hardy-Werbin, Max Rocha, Pedro P. Arpí Llucià, Oriol Taus García, Álvaro Nonell Mazelon, Lara, 1972- Duran Jordà, Xavier, 1974- Villanueva, Xavier Joseph-Pietras, Debora Nolan, Luke Danson, Sarah Griffiths, Richard López-Botet, M. (Miguel) Rovira Guerín, Ana Albanell Mestres, Joan Ottensmeier, Christian Arriola Aperribay, Edurne
author	Hardy-Werbin, Max
author_facet	Hardy-Werbin, Max Rocha, Pedro P. Arpí Llucià, Oriol Taus García, Álvaro Nonell Mazelon, Lara, 1972- Duran Jordà, Xavier, 1974- Villanueva, Xavier Joseph-Pietras, Debora Nolan, Luke Danson, Sarah Griffiths, Richard López-Botet, M. (Miguel) Rovira Guerín, Ana Albanell Mestres, Joan Ottensmeier, Christian Arriola Aperribay, Edurne
author_role	author
author2	Rocha, Pedro P. Arpí Llucià, Oriol Taus García, Álvaro Nonell Mazelon, Lara, 1972- Duran Jordà, Xavier, 1974- Villanueva, Xavier Joseph-Pietras, Debora Nolan, Luke Danson, Sarah Griffiths, Richard López-Botet, M. (Miguel) Rovira Guerín, Ana Albanell Mestres, Joan Ottensmeier, Christian Arriola Aperribay, Edurne
author2_role	author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Biomarkers Cytokines Immunotherapy Ipilimumab Small cell lung cancer
topic	Biomarkers Cytokines Immunotherapy Ipilimumab Small cell lung cancer
description	Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival. Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated. Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival. Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC.
publishDate	2019
dc.date.none.fl_str_mv	2019 2020
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion
format	article
status_str	acceptedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10230/44002 http://dx.doi.org/10.1080/2162402X.2019.1593810
url	http://hdl.handle.net/10230/44002 http://dx.doi.org/10.1080/2162402X.2019.1593810
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Oncoimmunology. 2019;8(6):e1593810
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Taylor & Francis
publisher.none.fl_str_mv	Taylor & Francis
dc.source.none.fl_str_mv	reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

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