The role of CD8+ regulatory T cells in anti-tumour immune responses in Hepatocellular Carcinoma

Li, Ka-Kit (2018). The role of CD8+ regulatory T cells in anti-tumour immune responses in Hepatocellular Carcinoma. University of Birmingham. Ph.D.

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Abstract

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.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):