CCBIO webinar: Arne Östman
Cancer-associated fibroblasts; novel subsets associated with tumor biology features, outcome and response to treatment
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden, and Centre for Cancer Biomarkers (CCBIO), University of Bergen
Cancer-associated fibroblasts (CAFs) constitute a prognosis-associated heterogeneous cell population occurring in most solid tumors. According to model studies, CAFs exert multiple regulatory functions including regulation of malignant cells, vascular cells and immune cells. In-depth profiling of CAFs in clinical samples thus appears as a valid strategy for biomarker identification and for discovery of novel associations indicative of clinically relevant cellular cross-talk.
Analyses of the CAF-markers PDGFaR and PDGFbR have demonstrated that these proteins are independently expressed, and abundance of these markers show differential prognosis associations indicating that they mark functionally distinct CAF subsets.
PDGFbR was also explored as a candidate marker for radiotherapy (RT) sensitivity through analyses of a randomized trial-derived breast ductal carcinoma in situ (DCIS) collection. Notably, significant interactions between marker and treatment was detected in the analysis in such a manner that PDGFbR-high breast DCIS displayed no significant benefit of RT. Ongoing analyses in a tissue collection of invasive breast cancer provides similar, but weaker, associations between RT benefit and high PDGFR expression in invasive breast cancer.
Ongoing studies using single-cell RNA sequencing of human colorectal cancer CAFs have identified two main classes, subdivided into five subsets with distinct and strong survival associations. Results from ongoing analyses regarding subset-specific associations with driver mutations and immune features will be discussed.
Finally, multiplex-staining has been employed on a large lung cancer collection. These ongoing studies are identifying novel multi-marker-defined CAF subsets showing compartment- and subset-specific survival associations. Also in this setting analyses are ongoing regarding associations with driver mutations and the immune system.
Collectively, studies provide novel evidence for clinically relevant heterogeneity of CAFs supporting the overall concept that these cells should be further explored for development of biomarkers of clinical utility and drugs with novel mechanisms of action.
Chairperson: Lars A. Akslen, CCBIO