Joint Oncology/IRDB Imperial Seminar Series, Thursday 27.10.22 @ 13.30, hosted by Professor Luca Magnani.
We are delighted to have Giovanni Ciriello who is Tenure-track Assistant Professor, Computational Biology & Cancer Genomics group in the Department of Computational Biology, University of Lausanne, Switzerland.
Abstract for Talk
Non-genetic routes of lung cancer evolution
The progression of several solid tumors from indolent to aggressive disease is often marked by morphological changes of cells and tissue architecture. The molecular processes underlying these changes remains however largely uncharacterized. We analyzed lung adenocarcinoma progression in multiple patients by histopathology guided multi-region sampling, selecting tumor regions characterized by distinct morphologies, or histologic patterns. Histologic patterns were not enriched for specific genetic features, but they activated remarkably different transcriptional programs reflecting both cancer cell intrinsic reprogramming and diverse interactions with the tumor microenvironment (TME). Even within the same tumor, we observed immune cold, inflamed, and excluded tumor regions, associated with specific histologic patterns. To further characterized cancer cell intrinsic features associated with disease progression, we integrated single cell RNA-seq data from 105 human lung adenocarcinoma samples for a total of ~500K cells. From this dataset, we unbiasedly determined multiple transcriptional programs that were differentially activated during tumor progression. These programs coalesced in four major cell states characterized by 1) lineage specific transcription factors, 2) activation of stress response pathways, 3) loss of lineage features and increased proliferative capacity, and 4) activation of angiogenic pathways and increased migratory potential. Lastly, using spatial transcriptomic profiles, we show that lung cancer cell states are associated with specific spatial niches and TME interactions. Overall, our results show that, independent of genetic features, cancer cell plasticity is a key driver of lung cancer progression.
This event will be hybrid.