Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis

Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses...

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Autores: Santisteban, Marta, Pérez Solans, Belén, Hato, Laura, Sánchez Bayona, Rodrigo, Idoate Gastearena, Miguel Ángel, Inogés, Susana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/136954
Acceso en línea:https://hdl.handle.net/11441/136954
https://doi.org/10.1177/17588359211064653
Access Level:acceso abierto
Palabra clave:Immunotherapy
Neoadjuvant
Early Breast Cancer
Dendritic Cell Vaccines
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spelling Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysisSantisteban, MartaPérez Solans, BelénHato, LauraSánchez Bayona, RodrigoIdoate Gastearena, Miguel ÁngelInogés, SusanaImmunotherapyNeoadjuvantEarly Breast CancerDendritic Cell VaccinesBackground: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p=0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p=0.25), 16.6% versus 0% in luminal B (p=0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p<0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p<0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-β repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. Trial registration: ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.SAGE JournalsCitología e Histología Normal y Patológica2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/136954https://doi.org/10.1177/17588359211064653reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)Ingléshttps://journals.sagepub.com/doi/10.1177/17588359211064653info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1369542026-06-17T12:51:07Z
dc.title.none.fl_str_mv Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
title Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
spellingShingle Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
Santisteban, Marta
Immunotherapy
Neoadjuvant
Early Breast Cancer
Dendritic Cell Vaccines
title_short Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
title_full Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
title_fullStr Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
title_full_unstemmed Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
title_sort Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis
dc.creator.none.fl_str_mv Santisteban, Marta
Pérez Solans, Belén
Hato, Laura
Sánchez Bayona, Rodrigo
Idoate Gastearena, Miguel Ángel
Inogés, Susana
author Santisteban, Marta
author_facet Santisteban, Marta
Pérez Solans, Belén
Hato, Laura
Sánchez Bayona, Rodrigo
Idoate Gastearena, Miguel Ángel
Inogés, Susana
author_role author
author2 Pérez Solans, Belén
Hato, Laura
Sánchez Bayona, Rodrigo
Idoate Gastearena, Miguel Ángel
Inogés, Susana
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Citología e Histología Normal y Patológica
dc.subject.none.fl_str_mv Immunotherapy
Neoadjuvant
Early Breast Cancer
Dendritic Cell Vaccines
topic Immunotherapy
Neoadjuvant
Early Breast Cancer
Dendritic Cell Vaccines
description Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p=0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p=0.25), 16.6% versus 0% in luminal B (p=0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p<0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p<0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-β repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. Trial registration: ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/136954
https://doi.org/10.1177/17588359211064653
url https://hdl.handle.net/11441/136954
https://doi.org/10.1177/17588359211064653
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://journals.sagepub.com/doi/10.1177/17588359211064653
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 SAGE Journals
publisher.none.fl_str_mv SAGE Journals
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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