I have generated a genetically engineered mouse model of colorectal cancer metastasis. To characterise the features of gamma/delta T cells in the mouse colorectal cancer metastasis model, I performed flow cytometry analysis on immune cells from the blood, lymph node, liver, small intestine and tumour. I revealed that these cells in the tumour are IL-17 positive, less activated and l have a less cytotoxic phenotype. I have generated a mouse model of colorectal cancer metastasis with lack of gamma/delta T cells. Also, I performed tumour organoid transplantation into the colons of gamma/delta T cell deficient mice to examine the effect of gamma/delta T cell loss in tumour growth. Using those models, I performed flow cytometry analysis to examine the number of neutrophils. The results showed that gamma/delta T cells promote tumour growth and neutrophil expansion. I have generated two other mouse cancer models without gamma/delta T cells. These two models develop only the primary tumours but not metastasis and these models are used to examine the role of BTNL1 in cancer development. I showed that BTNL1 does not affect tumour development. Taken together, these results suggest that gamma/delta T cells but not the intestine specific type of gamma/delta T cells control neutrophils in a mouse colorectal cancer model. Targeting gamma/delta T cells would be more beneficial than targeting neutrophils because gamma/delta T cells act upstream of neutrophil expansion. Also, neutrophil turnover is so quick (about 8 hours in humans) that clinical application would need frequent injection of depleting antibodies, while turnover of gamma/delta T cells is slow (turnover of T cells is months to years in humans). Those findings are still based on a mouse model, so my next step will be to determine whether this is the same in humans before clinical application.
To disseminate these findings, I have attended the National Cancer Research Institute Conference (November, 2018) and utilised this chance to network and exchange ideas with the speakers. I have also had opportunities to present my data at the ACRCelerate workshop (November, 2019), the Institute of Infection, Immunity & Inflammation seminar presentation (January 2019), the Edinburgh-Glasgow Joint Cancer Immunology Meeting (October 2018), 2 host Institute-internal seminars. Through this dissemination, I obtained new ideas and many suggestions from the audiences.
