Progress beyond the current state of the art and expected results
Recent research showed that when the tumour cells become resistant to immune cell attack, the consequence is not only that the immune system becomes ineffective, but in fact worse. This is because when immune cells try to kill the tumour cells via the DL-DR pathway, instead of cell death, it initiates tumour cell migration, potentially driving metastasis. The work of the DISCOVER programme will increase our understand how this process take place, and how it can be blocked.
In addition to the various impacts of death ligands on tumour cell fate, it is equally important to consider the role of death ligands in regulating the function of immune cells. While immune cells are essential to protect the organs and tissues from infections and from the spread of malignant cells, overfunction of immune cells cause autoimmune diseases by damaging otherwise healthy tissues. Thus, the number and activity of immune cells have to be tightly controlled. In this regard, the DL-DR system is known to limit the activity of immune cells and function to prevent autoimmunity. During tumour immune editing, it is not only the immune cells applying selective pressure on the tumour cells, but reciprocally, the tumour cells also sculpt the functionality of the immune cells.
However, our knowledge is very limited about how the DL-DR controls the function of immune cells in a tumour. Our hypothesis is that the DL-DR system may be a main driver of the equilibrium phase and the consequent escape phases by limiting the activity of the immune cells against tumour cells.
Potential impact DISCOVER research will make
DISCOVER will impact on the career development of both early stage and experienced staff by developing their skills, expertise and their personal collaborative networks thus enhancing both career aspects and career prospects by equipping our researchers with state-of-the-art scientific knowledge and technical skills, work experience in an international research consortium, intersectoral work experience and working in an environment stimulating creativity and entrepreneurship.
Combined, the scientific and technical skillset DISCOVER members will receive will enable them to become leaders in the field, either in the academic or in the industrial sector. The long-term impact of DISCOVER on staff members will be promotion of their development into scientists with key boundary-spanning capabilities, who are innovation-oriented and can contribute their enhanced creativity and resourcefulness to tackling unmet clinical needs in cancer research.
Producing highly skilled researchers with key transferable skills who are able to exploit their scientific knowledge in an innovative and entrepreneurial manner has the potential to promote the ERA to the forefront of research and innovation in tumour immunology, an area that has economic and societal significance because of the current unmet need for innovative therapies for a large number of cancer patients.
DISCOVER will also create impact by developing new and lasting research collaborations, achieving transfer of knowledge between participating organisations and contribution to improving research and innovation potential at the European and global levels
Overall, DISCOVER will exploit the multidisciplinary and cross-sectional expertise of the participants, establishes excellent research, training and networking programme with top calibre researchers to make leaps in scientific and clinical understanding and applications, which will push Europe to the forefront of cancer immunology, drive innovation capacity and competitiveness.
