dc.contributor
Institut Català de la Salut
dc.contributor
[Lodewijk I] Biomedical Research Institute I+12, University Hospital “12 de Octubre”, Madrid, Spain. Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain. Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain. [Bernardini A] Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain. [Suárez-Cabrera C] Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain. Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain. [Bernal E] Medical Oncology, University Hospital 12 De Octubre, Madrid, Spain. Medical Oncology, Infant Cristina University Hospital, Madrid, Spain. [Sánchez R] Medical Oncology, University Hospital 12 De Octubre, Madrid, Spain. [Garcia JL] Pathology Department, University Hospital 12 De Octubre, Madrid, Spain. [Rojas K] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Lodewijk, Iris
dc.contributor.author
Bernardini, Alejandra
dc.contributor.author
Suárez-Cabrera, C.
dc.contributor.author
Bernal, E.
dc.contributor.author
Sánchez-Bayona, Rodrigo
dc.contributor.author
Garcia, J. L.
dc.contributor.author
Rojas Laimito, Katerin Ingrid
dc.date.accessioned
2025-10-24T10:34:09Z
dc.date.available
2025-10-24T10:34:09Z
dc.date.issued
2022-10-18T12:19:03Z
dc.date.issued
2022-10-18T12:19:03Z
dc.date.issued
2022-01-27
dc.identifier
Lodewijk I, Bernardini A, Suárez-Cabrera C, Bernal E, Sánchez R, Garcia JL, et al. Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy. npj Precis Oncol. 2022 Jan 27;6:7.
dc.identifier
https://hdl.handle.net/11351/8311
dc.identifier
10.1038/s41698-021-00247-3
dc.identifier
000749220900001
dc.identifier.uri
https://hdl.handle.net/11351/8311
dc.description.abstract
Ovarian cancer
dc.description.abstract
Càncer d'ovari
dc.description.abstract
Cáncer de ovario
dc.description.abstract
Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.
dc.description.abstract
This study was funded by GlaxoSmithKline (GSK). I.L. position is funded by Fundación Científica Asociación Española Contra el Cáncer (AECC), Predoctoral AECC 2019 grant number PRDMA19024LODE. L. Morales position is funded by AECC, Postdoctoral AECC 2019 grant number POSTD19036MORA. This study was partially co-funded by European Regional Development Fund (FEDER) grants from Science and Innovation (SAF2015-66015-R and PID2019-110758RB-I00 to J.M.P.) and Instituto de Salud Carlos III (CIBERONC no. CB16/12/00228 to J.M.P.).
dc.format
application/pdf
dc.publisher
Nature Portfolio
dc.relation
npj Precision Oncology;6
dc.relation
https://doi.org/10.1038/s41698-021-00247-3
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Ovaris - Càncer - Tractament
dc.subject
Expressió gènica
dc.subject
Quimioteràpia combinada
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante
dc.title
Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
