Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy
| Autor: | I. Lodewijk, A. Bernardini, C. Suárez-Cabrera, E. Bernal, R. Sánchez, J. L. Garcia, K. Rojas, L. Morales, S. Wang, X. Han, M. Dueñas, J. M. Paramio, L. Manso |
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| Přispěvatelé: | Institut Català de la Salut, [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, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES] Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] Neoplasms. Tumors. Oncology. Including cancer and carcinogens Genetic Phenomena::Gene Expression [PHENOMENA AND PROCESSES] Ovaris - Càncer - Tractament neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Expressió gènica Quimioteràpia combinada Article Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Oncology Ovarian cancer terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] fenómenos genéticos::expresión génica [FENÓMENOS Y PROCESOS] RC254-282 |
| Zdroj: | NPJ Precision Oncology npj Precision Oncology, Vol 6, Iss 1, Pp 1-11 (2022) Scientia |
| ISSN: | 2397-768X |
| Popis: | Ovarian cancer Càncer d'ovari Cáncer de ovario 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. 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.). |
| Databáze: | OpenAIRE |
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