SCALTIE · Single cell analysis of the lung tumour-immune ecosystem: Developing new tools for effective immunotherapy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-06-01 → 2019-05-31
- EU contribution
- €170,509
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Single cell analysis of the lung tumour-immune ecosystem: Developing new tools for effective immunotherapy
Tumours evolve to evade immune surveillance through a series of immune suppression mechanisms. In line with this, cancer immunotherapies, in which the immune system is turned on against tumours, are currently revolutionizing cancer treatment. Unfortunately, still many cancer patients do not respond to immunotherapies. Therefore, there is an urgent need to develop new tools for effective immunotherapy in order to increase treatment response rate. However, current methods that investigate bulk populations of cells lack the resolution to identify and analyse the diverse subpopulations of cells and the unique pathways and checkpoints they activate within the tumour ecosystem. I proposed to dissect the interface between human tumor and the immune system by combining single-cell RNA-Seq, modeling approaches, advanced functional assays and mouse models. I believe this work will lead to a better understanding of tumour immunity and the development of novel therapies tailored to individual cancer patient. Our single cell analysis of melanoma tumor immune infiltrates reveals a CD8+ T cell population that displays a continuous progression from a transitional towards a dysfunctional state and a distinct population of CD8+ cytotoxic T cells that are not connected to the dysfunctional gradient. Early dysfunctional T cells show the highest level of proliferation and dysfunctional load is associated with tumor-reactivity.
Data: CORDIS, © European Union
Project objective
Tumours evolve to evade immune surveillance through a series of immune suppression mechanisms. In line with this, cancer immunotherapies, in which the immune system is turned on against tumours, are currently revolutionizing cancer treatment. Unfortunately, still many cancer patients do not respond to immunotherapies. Therefore, there is an urgent need to develop new tools for effective immunotherapy in order to increase treatment response rate. However, current methods that investigate bulk populations of cells lack the resolution to identify and analyse the diverse subpopulations of cells and the unique pathways and checkpoints they activate within the tumour ecosystem. I therefore aim to use advanced single cell genomic techniques for unbiased and high-resolution characterization of the different malignant, stromal and immune cell populations within the microenvironment of lung tumour, which is the biggest cancer killer in Europe. In combination with modelling approaches and advanced functional assays, I will identify subpopulations of cells specific to tumours, known and novel pathways mutated in tumour cells and cell-cell interactions that all together play crucial roles in the tumours pathogenicity. A comprehensive understanding of these processes provides the basis for understanding why existing cancer immunotherapies do not always succeed and provides new potential targets for the development of precise medicine tailored to individual patient. Complementary to my skills in molecular and cellular biology, I will acquire scientific skills in single cell genomics and bioinformatics, and soft skills in project management, mentoring, communicating, etc in this project. Those skills will enable me to establish my own research group in the near future to investigate the interface between the immune system and tissues under health and diseases with holistic approaches, which is my long-term career goal.
Original text from CORDIS.
Participants
- WEIZMANN INSTITUTE OF SCIENCE · RehovotCoordinatorIsrael
Links
Data: CORDIS, © European Union