Abstract 14P
Background
Non-epithelial ovarian tumours encompass a heterogeneous group of neoplasms comprising germ cell tumours (GCT) and sex-cord stromal tumours (SCST). These tumours are characterized by an extensive inter- and intratumoral heterogeneity. To better understand the landscape of immune cells in non-epithelial ovarian cancer, we construct a blueprint of stromal heterogeneity using single-cell RNA sequencing (scRNA-seq).
Methods
We performed scRNA-seq of 66 919 cells from fresh tissue collected from 12 patients, both in primary and recurrent setting. Most tissue samples were derived from SCST (n=9), including 7 adult granulosa cell tumours, 1 primary juvenile granulosa cell tumour and 1 primary Sertoli-Leydig cell (SL) tumour. Three samples were obtained from treatment-naïve GCT (2 immature teratomas (IT) and one dysgerminoma (DG)). We characterise immune cell subtypes phenotypically by highlighting its specific marker genes.
Results
Based on differential expression analysis and expression of transcriptomic markers, we identified 27 clusters consisting of 9 tumour cell and 18 stromal cell clusters. By clustering the transcriptome of 5961 T-cells and natural killer (NK) cells, T and NK cells deriving from DG (58%) and Sertoli-Leydig cell (20%) were found to be predominantly expressed. Remarkably, the DG tumour sample exhibited a pronounced cytotoxic environment, dominated by CD8+ exhausted T-cells whereas in the SL tumour a more naïve condition was observed. Half of the B-cells, mainly in differentiated cell states, derived from the DG sample. A nearly absence of B cells in all granulosa cell tumors. Regarding the myeloid lineage, the granulosa cell samples were dominated by LYVE1 and CX3CR1 macrophages. The latter are known to be inversely correlated with T cell expansion and thus predictors of low response to anti-PD-1 treatment.
Conclusions
With this analysis, we generate a comprehensive blueprint of the tumour micro-environment in non-epithelial ovarian cancer. Despite a limited sample size, we obtain high-resolution insights. The cytotoxic environment of dysgerminoma and immune desert profile of granulosa cell tumours are novel findings, which, however, need to be validated in larger datasets.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Loverix: Financial Interests, Institutional, Invited Speaker, 2021 and 2022: AstraZeneca; Financial Interests, Institutional, Invited Speaker - institutional fee: GSK; Financial Interests, Personal, Invited Speaker, Reimbursement of travel/conference fee: Twist Biosciences; Financial Interests, Personal, Other, Non-profit Organisation FWO - Research Foundation Flanders - PhD Scholarship Strategic Based Research since November 2020: FWO Research Foundation Flanders. T. Van Gorp: Financial Interests, Institutional, Advisory Board, Apr-2021 until present: MSD; Financial Interests, Institutional, Advisory Board, May-2021 until present: GSK; Financial Interests, Institutional, Advisory Board, Feb-2021: OncXerna Therapeutics; Financial Interests, Institutional, Advisory Board, Jan-2021: Eisai; Financial Interests, Institutional, Advisory Board, Jan-2021 until present: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Apr 2022: GSK; Financial Interests, Institutional, Research Grant, Oct-2020 until Oct-2021: Amgen; Financial Interests, Institutional, Research Grant, Oct-2020 onwards: Roche. I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd. (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd. (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc. (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). All other authors have declared no conflicts of interest.