GDCOLCA · Understanding gamma delta T cells in colon cancer metastasis

Understanding gamma delta T cells in colon cancer metastasis

Colon cancer is a leading cause of death worldwide and over 370,000 new cases are diagnosed each year in countries of the European Union. Early-stage colon cancer is curable but there is no effective therapy for metastatic disease. Strikingly, less than 10% of patients with Stage IV metastatic disease live beyond 5 years. As such, the development of an effective therapy for metastatic cancer is desired. For this, understanding the mechanisms of metastasis is essential. So far, much of the work in metastasis biology has focused on how cancer cells develop and acquire a metastatic phenotype. However, the role of the immune system during the metastatic process has received far less attention and is largely unknown. Immune cells can both promote and prevent metastasis. Immune cells have been shown to participate in each step of the metastatic cascade, including formation of the pre-metastatic environment. Recent studies have provided new insights about two particular types of immune cells, called neutrophils and gamma/delta T cells. Also, IL-17, an important pro-tumour cytokine produced from gamma/delta T cells, links neutrophils and gamma/delta T cells. Recently, a novel molecule called BTNL1 has been reported as a critical activator of intestine specific gamma/delta T cells. The role of BTNL1 has not previously been investigated in any cancer models. The gamma/delta T cells-IL-17-neutrophil axis was recently shown by my host institute supervisor to promote breast cancer metastasis. However, the significance of this axis in other cancers’ metastasis remains unaddressed. In this action, my objectives were to : 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 mouse colorectal cancer metastasis 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. So, my goal was to understand the role of these gamma/delta T cells in colon cancer development and metastasis. I have achieved most of the objectives during the action period. I have revealed the characteristics of gamma/delta T cells in colorectal cancer metastasis. I have assessed the requirement of gamma/delta T cells in colorectal cancer metastasis and neutrophil expansion. I have also examined role of BTNL1 molecule in colorectal cancer development. The involvement of BTNL1 in colorectal cancer metastasis has not been addressed and I am still working on this aspect. These achievements clarified the significance of gamma/delta T cells in colorectal cancer development and metastasis and identified potential targets for immunotherapy that may help patients with metastatic colon cancer in future.

Data: CORDIS, © European Union