Microenvironment cell populations are associated with clinical outcomes in high-grade serous ovarian cancer

Rachel Watson; Katharine Linder; Sofia Gabrilovich; Keely Ulmer; Andrew Polio; Michael Goodheart; David Bender; Jesus Gonzalez Bosquet

doi:10.1016/j.ygyno.2024.07.284

Objectives Multiple studies have reported associations between ovarian cancer prognosis and the composition of the tumor microenvironment, including the extent of infiltrating immune cells and fibroblasts. We hypothesized that microenvironment cell populations (MCP) affect clinical outcomes in high-grade serous ovarian cancer (HGSOC). Methods This was a case-control study comparing the microenvironment of HGSOC samples (cases, n = 112) with normal fallopian tube samples (controls, n = 12) collected at the time of surgery. Variables included age, BMI, Charlson comorbidity Index, CA-125, and clinical outcomes, such as response to chemotherapy, optimal cytoreduction, and survival. We assessed the association of MCP with clinical outcomes and validated the results with The Cancer Genome Atlas (TCGA) HGSOC data. MCP-counter (an R package) was used to quantify the abundance of immune and non-immune stromal cell populations from RNAseq of heterogeneous tissue samples. MCP-counter scores were then used for further analyses and comparisons. Univariate and multivariable regression modeling was performed to determine the association between clinical outcomes and proportions of immune cells or MCP scores. Initial univariate analyses were performed between cases and controls to select significant variables (clinical and MCP scores) that would be introduced into multivariate models. Statistical significance at P < 0.05. Results In multivariate analysis, samples with HGSOC had significantly less infiltration of B cells (P = 0.017) and neutrophils (P = 0.038) than tubal samples. After accounting for significant clinical variables (age and neoadjuvant chemotherapy) in the multivariate analysis, patients with higher CD8 T cell MCP scores responded significantly better to chemotherapy (P = 0.034). After accounting for other clinical variables (disease in the chest), the only independent variable associated with optimal cytoreduction in the multivariate analysis was the sample's cytotoxic lymphocytes MCP score (P = 0.004): patients with a higher score had better chance of optimal cytoreduction. After accounting for clinical variables, patient samples with higher fibroblast MCP scores had lower overall survival (P = 0.011). In the TCGA HGSOC dataset, we confirmed that HGSOC had significantly less infiltration of B cells, that samples with higher fibroblast infiltration had less overall survival, and, despite not being significant, samples with higher CD8 T cells MCP score responded better to chemotherapy. Conclusions MCP are associated with the clinical outcomes of HGSOC patients. Further analysis is needed to determine if MCP, alone or in combination with other pathologic/genomic features, could predict tumor behavior at an individual level.

Microenvironment cell populations are associated with clinical outcomes in high-grade serous ovarian cancer

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