1. 415 Single-cell map of the dynamic changes underlying platinum-based chemotherapy with or without bevacizumab in high-grade serous tubo-ovarian carcinoma
- Author
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A Vandestichele, T Van Gorp, Sileny Han, E Van Nieuwenhuysen, T Laga, Liselore Loverix, D Lambrechts, Ignace Vergote, Siel Olbrecht, A.S. Van Rompuy, Pieter Busschaert, and Thaïs Baert
- Subjects
Chemotherapy ,Stromal cell ,Bevacizumab ,business.industry ,Angiogenesis ,medicine.medical_treatment ,medicine.disease ,Vascular endothelial growth factor ,Serous fluid ,chemistry.chemical_compound ,Vascular endothelial growth factor A ,chemistry ,Cancer research ,Carcinoma ,medicine ,business ,medicine.drug - Abstract
Introduction/Background* The vascular endothelial growth factor (VEGF) plays an import role in emergence and spread of high-grade serous tubo-ovarian carcinoma (HGSTOC). Bevacizumab, a monoclonal antibody targeting VEGFA, has therefore been added to first-line treatment of advanced HGSTOC. We here map the dynamics of different stromal components of the tumour microenvironment under chemotherapy with or without bevacizumab. Methodology We performed single-cell RNA-sequencing on 62,461 cells sampled from 6 HGSTOC patients before and after neo-adjuvant platin-based chemotherapy with or without bevacizumab. We identified 44 stromal cell subclusters on which we applied Mixed-effects modelling of Associations of Single Cells to identify cell populations associated with bevacizumab exposure and pathological response using the chemotherapeutic response score. Result(s)* Our study revealed diverse stromal cell subsets associated with bevacizumab exposure. The addition of bevacizumab to frontline chemotherapy increased the odds of endothelial cell (ECs) prevalence by a 3-fold (OR 2.91, 95%CI:2.36-3.58; p Conclusion* We here provide initial evidence on the mechanisms underlying early response to bevacizumab and frontline chemotherapy in HGSTOC, including tip cell impairment, reduced hypoxia and a decrease in regulatory T cells. However, bevacizumab exposure increased the influx of PDGFC-expressing macrophages capable to bypass VEGFA-dependent angiogenesis.
- Published
- 2021