milieuPCa · Defining the immunosuppressive milieu of prostate cancer with single cell Omics technologies
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-05-01 → 2025-12-29
- EU contribution
- €174,806
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Defining the immunosuppressive milieu of prostate cancer with single cell Omics technologies
In recent years, novel immunotherapies, such as antibodies targeting immune checkpoints or CAR T cells, have revolutionized the way cancers are treated. Nonetheless, the treatment of solid tumors has remained challenging, inter alia due to the small number of tumor-infiltrating T lymphocytes or their inactivity in the immunosuppressive tumor microenvironment (TME). Prostate cancer is among the most common tumors in men. While early stages can be successfully managed by surgery or radiation, no curative treatment exists for advanced stages. Here, we aimed at understanding the immune milieu of prostate cancer by employing bulk and single cell high-throughput sequencing on prostatectomy samples in order to obtain a comprehensive view of the immunosuppressive mechanisms in prostate carcinoma. RNAseq data was collected for both tumor and normal adjacent regions from about 30 prostate cancer samples. Single cell data was collected for a subset of patients to have a deeper view of where the signal comes from. Integration of data obtained from these analyses is enabling us to improve our understanding of the complex interplay between the immune system and tumor cells. These data will moreover provide a potent source for translational studies to diagnose and treat prostate cancer. The project has been early terminated because the research fellow accepted a industry job offer. There are no publications yet, because data was collected until the research fellow left; however, a manuscript is in preparation.
Data: CORDIS, © European Union
Project objective
The immune contexture of prostate cancer is poorly studied, despite among researchers there is a strong interest in developing immunotherapy approaches to cure the disease. It is known that the immune system can have a dual role in the tumor progression, in other words, it can either promote or suppress tumor growth and invasion. However, the immunomodulation of prostate cancer and the immunosuppressive mechanisms involved are still not entirely known. In this proposal, I suggest using and integrating Omics data from various sources to give a holistic and comprehensive overview of the immune milieu of prostate cancer at a single cell level. Human prostate cancer samples will be used to generate transcriptomics with scRNA-Seq, epigenomics with scATAC-Seq and multiplexed images with the Hyperion system. Transcriptomics and epigenomics data at the single cell level will allow the classification of the cell types at the molecular level, the delineation of related biomarkers and biological mechanisms as well as the establishment of a prostate cancer specific deconvolution approach. Spatial information will be obtained for candidate biomarkers found through scRNA-Seq and scATA-Seq, and all data will be then integrated in order to create a link between transcriptional regulation, signaling pathways and cell-cell interaction. High throughput data integration in prostate cancer will allow elucidation of the biological mechanisms involved in an unprecedented level. This study will be a powerful resource for future basic studies on prostate cancer, but also for guiding the development of novel immunotherapy approaches.
Original text from CORDIS.
Participants
- UNIVERSITAETSKLINIKUM FREIBURG · FreiburgCoordinatorGermany
Links
Data: CORDIS, © European Union