Introduction/Background Despite substantial progress in high-grade serous ovarian cancers (HGSOC) in recent years, the prognosis remains poor. While ascites play a significant role in HGSOC progression, their immune landscape characterization is essential to understand their impact on the immune cell response.
Methodology Ascites were collected during initial laparoscopy for advanced HGSOC and then processed, using respective multiplexed approaches of flow cytometry-based marker expression analysis and quantitation of mediators, for profiling immune cellular and cell-free fractions. Furthermore, ascites fluids were functionally screened for their biological effects on healthy monocytes, undifferentiated and under M1-polarization.
Results 20 HGSOC patients were included from September 2020 through November 2022. Median age at diagnosis was 68 years (50–73). 19 patients had stage IIIC or IV HGSOC. 7 patients had debulking surgery (2 primary DS). After a median follow-up of 13 months (5–30), median progression-free survival was 11,0 months (95% confidence interval 7,9 – 14,1). At the time of analysis 7 patients had died.
Ascites were mostly ‘enriched’ in regulatory immune cells including T and myeloid populations. T cells highly expressed immune checkpoints e.g. PD1 in T cells and TIGIT in Tregs. CD163+ TAMs were shown to express Arg1, CCR8, CCR2, and iNOS. While acellular fluids exhibited differentially-elevated levels of soluble mediators, functionally, they polarized monocytes into M2 macrophages, and even opposed their M1 polarization to switch to M2-status.
Conclusion HGSOC ascites harbor an altered immune environment where suppressive cells and mediators lead to immune cell dysfunction. Identification of ascites subgroups most favorable to the M2 phenotype would suggest a population with poor outcomes.
These findings highlight HGSOC ascites as a valuable tool for the identification of new immuno-oncological targets.
Disclosures I. Nafia, A. Chaibi and A. Bessede are employees of Explicyte Immuno Oncology.
G. Babin received personal fees from MSD and GSK
A. Italiano received research grants from AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Merck, MSD, PharmaMar, Novartis and Roche and received personal fees from Epizyme, Bayer, Lilly, Roche and SpringWorks.
C. Lebreton received personal fees from Clovis oncology, EISAI, MSD and GSK
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.