Analysis of tumor microenvironment changes after neoadjuvant chemotherapy with or without bevacizumab in advanced ovarian cancer (GEICO-89T/MINOVA study)
Beatriz Tavira 1 , Teresa Iscar 2 , Luis Manso 3 , Ana Santaballa 4 , Marta Gil-Martin 5 , Yolanda García García 6 , Margarita Romeo 7 , Maria Iglesias 8 , Ana de Juan Ferré 9 , Maria Pilar Barretina-Ginesta 10 , Aránzazu Manzano 11 , Lydia Gaba 12 , María Jesús Rubio 13 , Carlos E de Andrea 14 , Antonio González-Martín 15
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: Immunohistochemistry and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 ovarian cancer patients 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 effector/regulatory cells 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 (macrophages-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significative associated with PFS.
Conclusions: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at cellular level, changes in CD4+, CD8+lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. Based on 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 of advanced EOC.
CITATION Clin Cancer Res. 2023 Aug 1;CCR-23-0771. doi: 10.1158/1078-0432.CCR-23-0771