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Title: The role of CD8+ regulatory T cells in anti-tumour immune responses in hepatocellular carcinoma
Author: Li, Ka-Kit
ISNI:       0000 0004 6494 9231
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2018
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Tumour specific effector T-cells can be detected in the blood and tumours of patients with hepatocellular carcinoma (HCC) but fail to mount effective immune responses. Attempts to amplify anti-tumour immune responses using immunotherapy show promise, but are hampered by the presence of suppressive regulatory T-cells (Treg) that inhibit anti-tumour immune responses. Many different subsets of Treg have since been identified including regulatory T-cells expressing the surface marker CD8 (CD8⁺Treg). A set of experiments was designed in an attempt to increase our understanding on how CD8⁺Treg may disrupt anti-tumour response and by what mechanisms they are induced. CD8⁺Treg was analysed by isolation of liver-derived T-cells from human HCC. Monocyte-derived dendritic cells (moDC) matured with tumour tissue conditioned medium were used to assess they potential to induce CD8⁺Treg. CD8⁺Treg infiltrating HCC demonstrated a suppressive phenotype. The co-culture of naïve CD8⁺T-cells with tumour-conditioned moDC induces a population of CD8⁺Treg through an IDO dependent mechanism. This population of induced T-cells was able to suppress via the CD39-adenosine pathway. The findings of the mechanisms involved in the induction of CD8⁺Treg by DC and the involvement of CD39 in the suppressive capacity of these novel T-cells, may guide the development of future immunotherapeutic in HCC.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR180 Immunology ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)