幸运飞艇计划

罢补濒办:听Spatially enriched multi-marker human CAF-subsets linked to treatment response, prognosis, driver mutations, immune features and micro-niches

Speaker: Arne 脰stman,听professor at the听Karolinska Institute (KI) in Sweden and part of the听international faculty at CCBIO.听Professor 脰stman鈥檚 research is听focused on the biology of the tumor听microenvironment with special focus on听tumor associated fibroblasts and their听role in cancer progression.听脰stman was vice-coordinator of听STRATCAN, a government funded听initiative for development of excellent听cancer research at KI (2010-2018) and听acted as coordinator for the Swedish听Research Council-supported STARGET听center-of-excellence 2006-16. Since 2020,听he is a member of the Nobel Assembly.
Through his international faculty听position at CCBIO, 脰stman has obtained听funding from the Norwegian Cancer听Society (NCS) and from Helse-Vest, for听projects on identification of novel tumor听stroma-derived biomarkers in breast听cancer. In this area, collaborative studies听with Professor Lars A. Akslen have led听to patent applications and ongoing听commercial development of findings.听Ongoing collaborative projects exploit听imaging mass cytometry for discovery听of novel breast cancer niches with drug听target and biomarker potential. Together听with Akslen, 脰stman is also involved听in collaborative tumor tissue profiling听studies with Teijo Pellinen at the FIMM听institute in Helsinki.

Host:听Lars A. Akslen
Where:
When: October 26, 2023 at 14.30-15.30

No registration necessary.听

础产蝉迟谤补肠迟:听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 鈥渃onsensus CAF subsets鈥� 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 (鈥淓uroCAF group鈥�, 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).听

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).听

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.

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