182P - Exploring Cross-Compartmental Tumor Cell Plasticity and Immunogenicity in Serous Ovarian Cancer

Background

Ovarian cancer (OvCa) is one of the most prevalent cancers affecting women, with 5-year survival rates below 40%. Thus, it becomes imperative to deepen our comprehension of disease heterogeneity and progression. Within this context, the extraction of tumor cell aggregates from the solid tumor mass and the ascitic fluid offers a unique opportunity for a direct comparison of the two compartments. The identification of immune targets could provide guidance for immunotherapeutic strategies in the management of recurrent OvCa.

Methods

As part of debulking surgery, samples of solid tumor tissue and ascites were obtained from a cohort of 16 patients diagnosed with serous OvCa. Cell aggregates (ø 40-100μm) were isolated and cryo-preserved. Afterwards, specimens were subjected to a multi-parametric flow cytometric analysis, encompassing markers related to tumor (stem) characteristics and immunological features. Samples were scored by expression of plasticity markers (CD10, CD24, CD90, CD133) and immune markers (PD-L1, PD-L2, PVR, PVRL2, CD47, Calreticulin, CD39, CD73, HLA-A/B/C, HLA-DR/DP/DQ) were compared between groups of varying plasticities.

Results

Overall, ligands for co-inhibitory T-cell-receptors PD-L1 and PVR, as well as phagocytosis-associated molecules CD47 and Calreticulin were more highly expressed by tumor cells isolated from ascites, rather than solid tumors. Furthermore, EpCAM+ tumor cell subsets displaying ≥1 plasticity marker showed significantly higher levels of the investigated immunological targets. These findings were confirmed in a set of matched samples (n=4).

Conclusions

Our data indicates elevated levels of plasticity in cell aggregates derived from solid tumors. Immunogenicity markers, however, were more abundantly expressed by ascites-derived tumor cells. Given the frequent association of ascites with the dissemination and recurrence of OvCa, individuals with advanced-stage disease may benefit most from personalized immunotherapeutic interventions. Functional testing using patient-specific co-cultures of ascites-derived cell aggregates and immune cells could offer a path toward pre-therapeutic identification of patients, likely to respond to immunotherapeutic treatments.

Legal entity responsible for the study

The authors.

Funding

2cureX GmbH and BMBF funding.

Disclosure

L.S. Hell, T. Sturmheit, J. Kupper: Financial Interests, Personal, Full or part-time Employment: 2cureX GmbH. W.M. Fiedler: Non-Financial Interests, Personal, Other: AbbVie; Financial Interests, Personal, Research Grant: Amgen, Pfizer. B. Schmalfeldt: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, MSD, Eisai, GSK, Olympus; Financial Interests, Personal, Research Funding: Roche, MSD, GSK, AstraZeneca. All other authors have declared no conflicts of interest.