Objective Cancer is the leading cause of death in the world. Immunotherapy is having a major impact in counteracting these cancer-related deaths, since the activity of anti-tumour immune cells can be enhanced to kill cancer. Unfortunately, immunotherapy does not work for every patient, so we must understand how other immune cells participate in cancer progression to design new immunotherapies that may benefit a greater number of patients. One particular type of immune cell, called gamma/delta T cells, was recently shown by my Host to promote breast cancer metastasis via IL-17, an important pro-tumour cytokine. However, the significance of gamma/delta T cells and IL-17 in other cancer metastasis settings remains unclear. In this proposal, I will address this point using a newly developed sophisticated colorectal cancer metastasis model. This novel mouse model shows 100 percent penetration of metastasis, of which 80 percent is to the liver, similar to human colorectal metastasis. Using this metastasis model, I will: 1. Clarify characteristics of gamma/delta T cells in colorectal cancer metastasis, 2. Assess if depletion of gamma/delta T cells by a neutralizing antibody as well as crossing the model with gamma/delta T cell-deficient mice would reduce the occurrence of metastasis, and 3. Examine the involvement of BTNL1, which is a specific activator for anti-tumorigenic IFN-producing gamma/delta T cells in the intestine. The role of BTNL1 in any cancer setting and the importance of IL-17-producing gamma/delta T cells in colon cancer metastasis is largely unexplored. Addressing our goal to understand the role of these gamma/delta T cells in colon cancer metastasis, I will newly acquire expertise and technical skills in both immunology and cancer biology as well as have experience in excellent collaboration with several laboratories. This proposal will identify additional targets for immunotherapy that may help patients with metastatic colon cancer. Fields of science medical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesclinical medicineoncologycolorectal cancermedical and health sciencesbasic medicineimmunologyimmunotherapy Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2017 - Individual Fellowships Call for proposal H2020-MSCA-IF-2017 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator BEATSON INSTITUTE FOR CANCER RESEARCH LBG Net EU contribution € 195 454,80 Address SWITCHBACK ROAD GARSCUBE ESTATE G61 1BD Bearsden United Kingdom See on map Region Scotland West Central Scotland East Dunbartonshire Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 195 454,80
