A Computational Cancer & Immunology lab at the McArdle Laboratory for Cancer Research

Josh’s paper, characterizing immune microenvironment of fallopian tubes and their impacts to ovarian cancer, is published.

We employed a data science approach to reanalyze 88 scRNA-Seq datasets across 58 donors, including FTs, HGSC tumors, and relevant adjacent and normal tissues. Integrated bioinformatics analysis on the comprehensive datasets led to the following findings, published in iScience:

  • We defined the heterogeneity of immune and stromal cell compartments with a depth that has not been reported. The observation is consistent between two independent FT scRNA-Seq datasets.
  • We bioinformatically identified the changes in monocytes and macrophages in cell composition and cellular interactions. Specifically, we observed the ratio of macrophages to monocytes is significantly increased from benign -> normal -> low-grade tumor -> high-grade tumors with more monocytes → more macrophages. Further analyses have provided supporting evidence that this increase might be linked with HGSC development, including pathway enrichment and Ligand-Receptor interactions.
  • We also identified monocyte and macrophage gene signature changes in FTs of donors with BRCA1/2 germline mutation who are at risk of developing HGSCs, as well as HGSC patients treated with chemotherapy from publicly available data.
  • Last, we characterized in detail the diversity of stromal cells (fibroblast, smooth muscle, and pericytes) in the FTs with two subsets (fibroblast expressed Complement C7 and smooth muscle cells) associated with the mesenchymal molecular HGSC, the worst prognosis subtype.