Understanding Long-Term Survival of Patients with Ovarian Cancer-The Tumor Microenvironment Comes to the Forefront.

High-grade serous ovarian cancer (HGSOC) is the deadliest subtype of ovarian cancer, and most patients do not survive more than 5 years after diagnosis. Yet, for reasons that are often elusive, approximately 15% of women with advanced-stage HGSOC will survive longer than 10 years. An understanding of the biological basis of long-term survival with HGSOC may elucidate novel prognostic factors and targets for treatment. Past analyses of the clinicopathologic features of these women and genetic profiles of their tumors have not revealed a unifying explanation for their increased longevity. In this issue of Cancer Research, Ferri-Borgogno and colleagues investigate the tumor microenvironment (TME) in samples from both long- and short-term survivors using spatial transcriptomics and single-cell RNA sequencing. They found that, in metastatic tumors, various populations of cancer-associated fibroblasts (CAF) in the TME play different roles in supporting the malignant phenotype of ovarian cancer cells. Higher density of CAFs, particularly αSMA+VIM+PDGFRβ+ CAFs, was associated with lower tumor immune infiltration and short-term survival. There was also marked expression of periostin and CD36 in spatially resolved CAFs, as well as a prevalence of the APOE-LRP5 ligand-receptor pair at the tumor-stromal interface in tissue from short-term survivors. These findings suggest that, in short-term survivors, CAFs are able to more effectively promote tumorigenicity, stemness, and chemoresistance in the nearby tumor. See related article by Ferri-Borgogno et al., p. 1503.