Immune Infiltrate Dynamics in Cancer Progression
Abstract
The goal of this project is to systematically characterize immune cell enrichment in the microenvironment of ovarian cancers and identify immune cell subsets that are prognostically relevant for patient care and/or can be used to develop more effective therapies targeting the tumor microenvironment. The two main cell types in the tumor microenvironment are fibroblasts and immune cells. An increased presence of fibroblasts is typically associated with poor prognosis while an increased presence of immune cells is an indicator of good prognosis. However, it is unclear if fibroblasts and immune cells affect prognosis independently or through an interdependent interaction. We first developed a computational model to identify immune cell types that are over-represented in fibroblast-rich tumors and under-represented in fibroblast-poor tumors. We found that fibroblast-rich tumors have an increased presence of pro-tumorigenic, and decreased presence of anti-tumorigenic, immune cells. Our comprehensive analyses of the tumor microenvironment in primary, metastatic, and recurrent ovarian tumors confirmed our hypothesis that fibroblasts alter the composition of immune cell infiltrates in tumors to tip the balance toward the pro-tumorigenic immune cell types. Our major finding from the correlative analysis of the tumor microenvironment with clinical outcomes is that the presence of CAFs negates the beneficial effects of immune infiltrates on patient survival.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2018
- Accession Number
- AD1059207
Entities
People
- Sandra Orsulic
Organizations
- Cedars-Sinai Medical Center