High-throughput profiling of the tumor microenvironment in Stage-I High-grade serous ovarian carcinoma

High-grade serous ovarian carcinoma is the most prevalent and lethal type of ovarian cancer in advanced stages. Remaining asymptomatic during its early phases the unclear factors contributing to tumor progression often led to delayed diagnoses, significantly amplifying its severity and mortality rates.1, 2 In advanced stages, the tumor manifests an immune-suppressive microenvironment, with a notable presence of immunosuppressive cells. This, coupled with molecular signals released by the tumor-cells themselves, creates an antagonistic environment that impairs the effectiveness of immune system.2-4 Nevertheless, the dynamic of immune suppression in the early tumor stages are still poorly understood. Herein, we delineated the transcriptional profiles of tumor-associated immune CD45+ cells and their CD45- counterpart, as well as matched blood circulating immune cells isolated from two incidentally diagnosed stage-I tumors without prior treatment. The comprehensive single-cell landscape of immune, stromal, and tumor cells revealed a highly immunosuppressive microenvironment that facilitates tumor progression. Specifically, an extensive remodeling of the immune cellular composition in the tumor microenvironment show an enrichment of suppressive CD4 T cells and tumor-associated macrophages, along with low cytotoxicity of natural killer cells and exhausted profile of CD8 T cells. Taking together, our findings highlight elevated immune cell heterogeneity in the microenvironment of the early stage-I tumor, providing a comprehensive map for designing novel treatment approaches.