2338P - The phenotype of tumor-associated macrophages in human high-grade serous ovarian carcinoma

Background

Ovarian cancer (OC) is one of the most common gynecological cancers, with the worst prognosis and the highest mortality rate. According to the FIGO, the overall five-year survival rate is approximately 50%. Tumor-associated macrophages (TAMs) are one of the most prominent populations of immune cells in both ovarian cancer tissue and malignant ascites. The most relevant task is to identify TAM subpopulations in ovarian cancer, to discover how they interact with chemotherapy and affect the development and outcome of the disease.

Methods

Patients with high-grade serous ovarian carcinoma were included in the study. FFPE samples with tumor were obtained after surgery. The study was carried out according to medical ethics. We applied two technologies of spatial transcriptomics for the analysis of TAM transcriptomic features in patients with ovarian cancer – 10x Genomics Visium and Nanostring GeoMX-DSP. All procedures were performed according to manufacturer`s protocols.

Results

The results of 10x Visium demonstrated that TAM cluster express CCL18, APOC1, GPNMB, LYZ, APOE, C1QC, C1QB, CTCB, SPP1, CTSS, and other genes. Interestingly, according to accumulating data the expression of these macrophage markers is distinctive feature for the potentially targeted population of lipid-associated TAMs. The morphology of macrophages in TAM cluster in clinical samples corresponds to the large lipid-associated TAMs. Nanostring technology allowed us to analyse ROIs with immune cells located in different tumor sites. The transcriptome of TAMs located near the tumor nest correlated to functional activation of extracellular matrix organization, antigen presentation, vascular development and myeloid leukocyte activation. These TAMs have the same morphology of large foamy macrophages and express APOE, SPP1, LYZ, CTSS, and other genes.

Conclusions

We found gene signature specific for the large TAMs in tumor tissue of patients with high-grade serous ovarian carcinoma.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Russian Science Foundation research project No 21-75-10021.

Disclosure

All authors have declared no conflicts of interest.