CCBIO Seminar – Arne Östman
Welcome to the CCBIO seminar series in the fall term of 2023. Speaker is Arne Östman from the Karolinska institute in Sweden. Open to all in auditorium 4, BBB. No registration necessary.
Main content
Talk: Spatially enriched multi-marker human CAF-subsets linked to treatment response, prognosis, driver mutations, immune features and micro-niches
Speaker: Arne Östman, professor at the Karolinska Institute (KI) in Sweden and part of the international faculty at CCBIO. Professor Östman’s research is focused on the biology of the tumor microenvironment with special focus on tumor associated fibroblasts and their role in cancer progression. 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.
Through his international faculty position at CCBIO, Östman has obtained funding from the Norwegian Cancer Society (NCS) and from Helse-Vest, for projects on identification of novel tumor stroma-derived biomarkers in breast cancer. In this area, collaborative studies with Professor Lars A. Akslen have led to patent applications and ongoing commercial development of findings. Ongoing collaborative projects exploit imaging mass cytometry for discovery of novel breast cancer niches with drug target and biomarker potential. Together with Akslen, Östman is also involved in collaborative tumor tissue profiling studies with Teijo Pellinen at the FIMM institute in Helsinki.
Host: Lars A. Akslen
Where: Auditorium 4, BB-building
When: October 26, 2023 at 14.30-15.30
No registration necessary.
Abstract: Tumor biology studies, mostly relying on mouse cancer models, imply functionally distinct subsets of cancer-associated fibroblasts (CAFs) impacting on malignant cells and immune cells. Also, studies in physiological settings uncover fibroblast subsets with instructive functions. Identification and molecular definition of clinically relevant CAF subsets are highly warranted. This presentation discusses studies towards the ultimate goal of identification of CAF subsets to be exploited as biomarkers or drug targets. A general theme of studies is in-depth analyses of clinical samples.
For the overall question of across-tumor-type consistent CAF subsets, an ongoing study is identifying “consensus CAF subsets” by integrated analyses of multiple single cell RNA seq data sets from mouse and human tumors of different cancer types. Interestingly, signatures representing emerging subsets also identify these subsets in external datasets from other tumor types (“EuroCAF group”, in prep.).
Regarding biomarker potential of CAFs, analyses of tissue samples from two randomized trials on radiotherapy (RT) identified associations between CAFs and RT benefit, such that high stromal PDGFRbeta expression is associated with reduced RT benefit. These findings have biomarker as well as combination therapy implications (Strell et al, Clin Can Res, 2021; Strell et al al, Br Can Res Treat, 2021).
For higher resolution in situ analyses of the human CAF landscape, multiplex-based profiling was done in two lung cancer collections, each with more than 300 cases, identifying 15 marker-defined CAF subsets. Two subsets, with contrasting expression of FAP and PDGFRA, showed significant and opposite associations with driver mutations, immune features and outcome (Pellinen et al, JNCI, 2023).
Finally, ongoing explorative studies in colorectal cancer (CRC), integrating single cell RNA seq and multiplex staining, identified four multi-marker-defined subsets. Preliminary analyses of six CRC cases show contrasting non-random spatial associations of these subsets with proliferating T-cells, with highly proliferative cancer areas and cancer areas with high T-cell infiltration. Analyses in a larger cohort of 200+ CRC cases are ongoing for validation of spatial properties and niche-associations of the subsets, and for analyses of outcome associations (Huang et al, in prep.).
Ongoing IMC-based characterization of the tissue architecture of breast cancer, with special focus on CAFs, will also be introduced.
Collectively, studies hopefully contribute to turning CAFs into a cell type of diagnostic and therapeutic significance.