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About the speaker
Anniina Färkkilä, MD PhD, is a gynecologist, an assistant tenure-track professor in translational gynecologic oncology, and a principal investigator at the Research Program in Systems Oncology, University of Helsinki, Finland. She completed her postdoctoral fellowship at the Dana-Farber Cancer Institute and Harvard Medical School in 2019, where her work focused on mechanisms of resistance and biomarkers for combination therapies in ovarian cancer. In 2018 she was awarded the Seth Wichmann award by the Finnish Gynecologic Society, and the Eero Saksela award by the Finnish Cancer Institute in 2022. She was the recipient of an ERC Starting grant in 2022. Currently, her laboratory focuses on understanding the complexity and cell-cell interactions in the tumor microenvironment using highly multiplexed imaging, advanced bioinformatics, and functional models in ovarian cancer. She is particularly interested in uncovering features that delineate the responses to novel combination- and immunotherapies.
Dr. Färkkilä also works as a specialist for gynecologic oncology at the Helsinki University Hospital (HUH), participating in multiple clinical trials at the HUH Comprehensive cancer center. Dr. Färkkilä coordinates the prospective Oncosys-Ova trial, and leads the Ovarian cancer project in the iCAN Digital Precision medicine Flagship. She is a board member at the Nordic Society of Gynecologic Oncology (NSGO), and the National Molecular tumor board of FINPROVE clinical trial by the Finnish Cancer Center (FICAN).
Abstract
The overall goals of our work are focused on elucidating the immune escape mechanisms in ovarian cancer through the application of multi-omics profiling and spatial biology, ultimately aiming to uncover new therapeutic targets and improve patient stratification in this highly aggressive cancer type. Our approach has focused on utilizing cutting-edge high-dimensional tissue imaging, single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and machine learning algorithms to capture comprehensive and actionable insights. In our recent work (Launonen et al Cancer Cell 2024) we subjected to multi-omics profiling, which integrated genomics, immune profiles, and spatial mapping of cellular populations. This allowed us to uncover spatially resolved immune dynamics within the tumor microenvironment (TME) and to analyze how various immune cells interact with tumor cells in both chemotherapy-sensitive and chemotherapy-resistant tumors. The resulting multi-omics dataset, consisting of over 25 million single cells, was instrumental in identifying key immune and stromal interactions. Through detailed analysis, we discovered the presence of Myelonets, which are networks of interconnected myeloid cells in close proximity to the tumor. These networks play a key role in driving CD8+ T cell exhaustion following chemotherapy. Our study demonstrated how these immune cell populations are spatially confined and modulated in response to chemotherapy, resulting in diminished anti-tumor immune activity and ultimately contributing to treatment resistance.
More recently, we developed a high-resolution single-cell spatial atlas analyzing 15.1 million cells from 280 advanced HGSC patients incorporating comprehensive clinical data and multi-level molecular profiling. By leveraging DNA methylation, gene copy number, and mutational profiling, we established clinicomolecular profiles that revealed critical tumor ecosystem dynamics. Our image analysis approach resolved the TME at the single-cell level, identifying coordinated multicellular domains associated with patient outcomes. We uncovered a pivotal role of cancer cell-intrinsic MHC class II (MHCII) expression at the tumor-stroma interface. We showed that MHCII-positive cancer cells create immune hotspots, marked by increased activation, impacting prognosis independently of clinicomolecular profiles.
The integration of spatial proteomics and transcriptomics has provided an unprecedented view of immune escape in ovarian cancer, revealing previously unrecognized spatial structures within the TME and pinpointing the specific interactions responsible for the suppression of effective anti-tumor immunity. This multi-disciplinary approach, combining genomic data, immune cell profiling, and spatial analysis, has given rise to a wealth of new information about how chemotherapy and immune escape mechanisms interact, offering key insights for advancing personalized medicine in ovarian cancer.
About the seminar series
Once a month, NCMBM invites international guest speakers to present on topics within molecular life science and medicine.
The seminar is open to all, with no registration needed.
Tea, coffee and a simple lunch will be served at 11.30 before the seminar.