CCBIO Seminar – Arne Östman

Speaker: Arne Östman, Department of Oncology-Pathology, Karolinska Institute (KI), Sweden, and CCBIO affiliated international investigator.

Title: "Cancer-associated fibroblasts; novel subsets associated with tumor biology features, outcome and response to treatment"

Place: digital event as webinar in Zoom. Link for audience: https://uib.zoom.us/j/65364409190?pwd=dDArejU0c3F6dWFRcFZwTVJjdGtDdz09    
If asked for passcode, use: N4qvm7nn
The link will be open from around 14:20, to allow time for audience to log on. We start at 14:30. Audio and video will be turned off for all audience, as default for safety reasons. We will unmute you if you have questions, after the talk. (Use the functions Raise Hands, or Q&A or Chat.) Make sure that you have not muted yourself, if you want to ask a question.

Time: January 28, 2021 at 14:30 (Norwegian time zone)

Chair: Lars A. Akslen

Short bio:

Professor Arne Östman received his PhD in 1990 on platelet-derived growth factor from the Ludwig Institute for Cancer Research, Uppsala University, Sweden. He is currently professor at the Karolinska Institute (KI).

Professor Östman’s research is focused on the biology of the tumor micro-environment with special focus on tumor associated fibroblasts and their role in cancer progression. Professor Östman was vice-coordinator of STRATCAN, a government funded initiative for development of excellent cancer research at KI (2010-2018), and acted as coordinator for the Swedish Research Council-supported STARGET center-of-excellence 2006-16. Since 2020 he is a member of the Nobel Assembly.

Abstract: 

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 appear 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 RT sensitivity through analyses of a randomized trial-derived breast DCIS collection. Notably, significant interactions between marker and treatment was detected in the analysis in such 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 seq of human colorectal cancer CAFs have identified 2 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. This 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 immune.

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.