Analysis of Tumor Microenvironment Changes after Neoadjuvant Chemotherapy with or without Bevacizumab in Advanced Ovarian Cancer (GEICO-89T/MINOVA Study)

Author:

Tavira Beatriz123ORCID,Iscar Teresa4ORCID,Manso Luis5ORCID,Santaballa Ana6ORCID,Gil-Martin Marta7ORCID,García García Yolanda8ORCID,Romeo Margarita9ORCID,Iglesias Maria10ORCID,de Juan Ferré Ana11ORCID,Barretina-Ginesta María Pilar12ORCID,Manzano Aranzazu13ORCID,Gaba Lydia14ORCID,Rubio María Jesús15ORCID,de Andrea Carlos E.416ORCID,González-Martín Antonio117ORCID

Affiliation:

1. 1Laboratory of Translational Oncology, Program in Solid Tumors, Cima-Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, Spain.

2. 2Navarra Institute for Health Research (IdISNA), Pamplona, Spain.

3. 3Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, Pamplona, Spain.

4. 4Department of Pathology, Cancer Center Clínica Universidad de Navarra, Madrid, Spain.

5. 5Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.

6. 6Department of Medical Oncology, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

7. 7Department of Medical Oncology, Institut Català d'Oncologia L'Hospitalet, Hospitalet de Llobregat, Spain.

8. 8Department of Medical Oncology, Parc Taulí Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain.

9. 9Department of Medical Oncology, Institut Català d'Oncologia Badalona, Badalona, Spain.

10. 10Department of Medical Oncology, Hospital Son Llátzer, Palma de Mallorca, Spain.

11. 11Department of Medical Oncology, Hospital Marqués de Valdecilla, Santander, Spain.

12. 12Department of Medical Oncology, Institut Català d'Oncologia Girona, Girona, Spain.

13. 13Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain.

14. 14Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.

15. 15Department of Medical Oncology, Hospital Universitario Reina Sofía, Cordoba, Spain.

16. 16Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.

17. 17Department of Medical Oncology, Cancer Center Clínica Universidad de Navarra, Madrid, Spain.

Abstract

Abstract 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

Funder

Roche España

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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