The role of T cells in ovarian cancer (#144)
Ovarian cancer (OC) tumours are immunogenic and lead to a low survival rate in patients. Survival rates remain low due to late stage diagnosis and disease relapse despite response to first line therapy. The tumour microenvironment is a contributor to the immunogenic attributes of OC and is composed of a vast array of cell types including T cells. Conventional and unconventional T cells have been found to have a role in OC development and progression making them the focus of this project. This project aims to determine the:
- Frequency, localisation, functional proficiency and protein signalling pathways of conventional T cells (CD4, CD8 and Tregs) in OC chemo-naïve patient samples compared to healthy female volunteers via flow cytometry, immunohistochemistry and immunofluorescence and protein analysis techniques;
- Frequency and functional proficiency of CD4, CD8 and Tregs in treatment respondent and non-respondent OC patient samples before and after treatment with maximum tolerated (MTD) or low dose dense (LDD) chemotherapy via flow cytometry techniques;
- Characterise unconventional MAIT cell biology via exploring their frequency, localisation, functional proficiency and genome differences in OC samples obtained from chemo-naïve, MTD and LDD patients, compared to healthy female volunteers via flow cytometry, immunohistochemistry, immunofluorescence and RNA sequencing techniques.
Immune escape has been reported in OC patients and is predictive of poor clinical outcome. This study will aid in understanding the biology of T cells across different FIGO stages, histological grades and Type I and Type II OC tumours. As the current first line chemotherapy treatments result in a low 5-year survival rate of 30-40%, this study may aid in developing T cell based immunotherapy targets for the improved treatment and diagnosis of OC patients.