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Analysis of Tumor Microenvironment Changes after Neoadjuvant Chemotherapy with or without Bevacizumab in Advanced Ovarian Cancer (GEICO-89T/MINOVA Study).
Tavira, Beatriz; Iscar, Teresa; Manso, Luis; Santaballa, Ana; Gil-Martin, Marta; García García, Yolanda; Romeo, Margarita; Iglesias, Maria; de Juan Ferré, Ana; Barretina-Ginesta, María Pilar; Manzano, Aranzazu; Gaba, Lydia; Rubio, María Jesús; de Andrea, Carlos E; González-Martín, Antonio.
Afiliación
  • Tavira B; Laboratory of Translational Oncology, Program in Solid Tumors, Cima-Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, Spain.
  • Iscar T; Navarra Institute for Health Research (IdISNA), Pamplona, Spain.
  • Manso L; Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, Pamplona, Spain.
  • Santaballa A; Department of Pathology, Cancer Center Clínica Universidad de Navarra, Madrid, Spain.
  • Gil-Martin M; Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.
  • García García Y; Department of Medical Oncology, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
  • Romeo M; Department of Medical Oncology, Institut Català d'Oncologia L'Hospitalet, Hospitalet de Llobregat, Spain.
  • Iglesias M; Department of Medical Oncology, Parc Taulí Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain.
  • de Juan Ferré A; Department of Medical Oncology, Institut Català d'Oncologia Badalona, Badalona, Spain.
  • Barretina-Ginesta MP; Department of Medical Oncology, Hospital Son Llátzer, Palma de Mallorca, Spain.
  • Manzano A; Department of Medical Oncology, Hospital Marqués de Valdecilla, Santander, Spain.
  • Gaba L; Department of Medical Oncology, Institut Català d'Oncologia Girona, Girona, Spain.
  • Rubio MJ; Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain.
  • de Andrea CE; Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
  • González-Martín A; Department of Medical Oncology, Hospital Universitario Reina Sofía, Cordoba, Spain.
Clin Cancer Res ; 30(1): 176-186, 2024 01 05.
Article en En | MEDLINE | ID: mdl-37527007
PURPOSE: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. EXPERIMENTAL DESIGN: IHC and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 patients with ovarian cancer enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. RESULTS: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells, and an upregulation in effector/regulatory cell ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophage-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significantly associated with progression-free survival (PFS). CONCLUSIONS: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at the cellular level, changes in CD4+, CD8+ lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. On the basis of our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T-effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first-line treatment of advanced epithelial ovarian cancer. See related commentary by Soberanis Pina and Oza, p. 12.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Terapia Neoadyuvante Límite: Female / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Terapia Neoadyuvante Límite: Female / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos