Regulatory T cell control of anti-tumour responses

Abstract

One of the main obstacles to immunotherapy of cancer in humans is the immunosuppressive environment that surrounds the tumour mass, preventing any effective immune response from halting or reversing the threat of the tumour. Thus the observations in Balb/c mice that CD25+ regulatory T cells (T regs) mediate suppression of antigen specific responses to CT26 and a number of tumours of distinct histological origin, was deemed worthy of investigation. The aim of this project was to examine in greater detail the immunosuppressive response generated by CT26, by using the irradiated tumour which we expected would represent an equivalent tumour challenge.

Overall the work described here indicates that, despite being essentially an equivalent antigen exposure, the response induced in the irradiated CT26 model is different to the live CT26 model. In the live CT26 model T reg depletion is critical to the survival of the tumour challenge, as well as the generation of the cross-protective response. In the irradiated CT26 model, the cross-protective response is not dependent on the T reg depletion, but the absence of T regs does boost the anti-CT26 response.

My second project sought to study tumour immunity in the context of the TAZ10 transgenic model of autoimmunity. The main conclusion from this project was that endogenous processing of the autoantigen TPO is dependent on the signal peptide, and at some point in the intracellular transport of TPO the pathway diverges into the pathway that allows the processing of TPO and the association of MHC class II molecules with TPO peptides, for recognition by CD4+ MHC class II restricted T cells.

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Identifiers

ORCID for Tim Elliott: orcid.org/0000-0003-1097-0222

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