Analysis of Tumor Microenvironment Changes after Neoadjuvant Chemotherapy with or without Bevacizumab in Advanced Ovarian Cancer (GEICO-89T/MINOVA Study)
Tavira, Beatriz (Clínica Universidad de Navarra)
Iscar, Teresa (Clínica Universidad de Navarra)
Manso, Luis (Hospital 12 de Octubre (Madrid))
Santaballa, Ana (Hospital Universitari i Politècnic La Fe (València))
Gil-Martin, Marta (Institut Català d'Oncologia - Hospital Duran i Reynals)
García García, Yolanda (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Romeo, Margarita (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Iglesias, Maria (Hospital Universitari Son Llàtzer (Palma de Mallorca, Balears))
de Juan Ferre, Ana (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Barretina-Ginesta, Maria-Pilar (Institut Català d'Oncologia)
Manzano, Aranzazu (Hospital Clínico San Carlos (Madrid))
Gaba, Lydia (Hospital Clínic i Provincial de Barcelona)
Rubio, Maria Jesus (Hospital Universitario Reina Sofía (Còrdova, Espanya))
de Andrea, Carlos E. (Centro de Investigación Biomédica en Red de Cáncer)
González-Martín, Antonio (Clínica Universidad de Navarra)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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. 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. 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). 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Clinical Cancer Research, Vol. 30 (august 2023) , p. 176-186, ISSN 1557-3265

DOI: 10.1158/1078-0432.CCR-23-0771
PMID: 37527007

11 p, 21.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles