Phenotyping Gamma Delta T cells in Bladder Cancer

Abstract

Event Abstract Back to Event Phenotyping Gamma Delta T cells in Bladder Cancer Magdalene Joseph1*, Fidelma Cahill2, Harriet Wylie2, Deborah Enting2, Mieke Van Hemelrijck1 and Adrian Hayday1 1 King's College London, United Kingdom 2 Guy's and St Thomas' NHS Foundation Trust, United Kingdom Background Bladder cancer is known to be immunologically modulated since the 1970s when Bacille-Calmette Guerin (BCG) was shown effective in treating superficial bladder tumours. Moreover, immune checkpoint inhibitors have now demonstrated survival benefit in advanced bladder cancer and are considered standard treatment for chemotherapy-resistant disease. Of special interest in immuno-oncology are unconventional, innate-like T cells bearing the gamma delta T cell receptor. They are found enriched at the epithelial surfaces and are capable of rapid, non-MHC restricted responses to various stressors. These cells are found to be the strongest correlate of positive prognosis in a recent transcriptomic analysis of over 18,000 tumours 1. Studies on mouse models of bladder cancer have shown that survival can be prolonged by injecting gamma delta T cells intravesically2 and that responses to BCG are abolished in gamma delta T cell knockout mice suggesting an anti-tumorigenic role3. This project aims to characterise the presence and phenotype of gamma delta T cells in the blood and tissue in human bladder cancer to understand their contribution to the immune regulation of the disease. Methods Mononuclear cells from peripheral blood of healthy, age-matched controls and patients with bladder cancer will be phenotyped by flow cytometry with a focus on gamma delta T cells to elucidate the differences between health and disease. Tissue infiltrating lymphocytes will also be isolated from bladder tumour tissue and peri-tumoural normal tissue using a cell-foam matrix culture system described previously4 and phenotyped in a similar fashion. Phenotypes from flow cytometry will be confirmed by polymerase chain reaction targeting the markers of interest. The localisation of gamma delta T cells within the tissue will be examined by immunohistochemistry. Results Preliminary results from healthy volunteers show differences in the expression of various markers between different gamma delta T cell populations and differences between fresh and frozen samples. Conclusion The aim is to understand gamma delta T cell mediated immune regulation of bladder cancer. Acknowledgements The King's Health Partners Urological Cancer Biobank and the King's College London Infectious Diseases Biobank for their help in obtaining patient and control samples. References