Dong Group

Our group focuses on determining the factors which affect T cells both in the control of viral infection and in the development of cancer. Within the context of cancer we aim to identify the factors affecting anti-cancer efficacy.

T cell (orange) killing a cancer cell (pink)T

Human infections, cancer development and the course of disease are mainly influenced by T cell responses. While a robust and appropriate T cell response is beneficial to the host, a weak or inappropriate response can be ineffective or even have a detrimental effect. Numerous factors influence the quality of the T cell response to viral infections or cancer development. Predominant among them being the microenvironment of the tumour or infection site, the type of cells affected and in the case of infection, the variability of the virus. By understanding the key factors required for efficient control by the T cell response in a number of different viral infections and viral associated cancers, we aim to identify targets to augment and control the immune response as a way of improving the outcome of in several important human diseases.

As a group we are focussing our expertise in both a cancer and viral infection setting to:

1. Assess the function and dysregulation of cancer-specific T cells

2. Identify inhibitory and co-stimulatory factors that affect anti-cancer efficacy

3. Determine the role of the anti-viral protein IFITM3 in Hepatitis B virus-induced liver cancer

4. Determine the mechanism of IFITM3-viral restriction in the context of Influenza virus

5. Assess the role of T cells in Influenza virus infection and the factors that affect their function

In cancer, it is known that T cell responses are diminished but the mechanisms behind this remain unclear for some cancers. While immune checkpoint inhibitors are proving successful in the clinic for some cancer patients, others see no impact of these immunotherapy treatments. The factors that determine which patients will or won't respond to treatment are unclear. Through characterisation and identification of inhibitory and co-stimulatory factors in association with studies on the function of cancer-specific T cells we aim to identify novel targets and strategies for immunotherapy.

Our group have previously identified a single nucleotide polymorphism (SNP) within the anti-viral restriction protein IFITM3 which increases the severity of influenza A virus infection and accelerates the progression to AIDS in HIV-1 infection. IFITM3 is known to restrict more than 15 RNA viruses, but the mechanism of how this occurs is unknown. Elucidating this mechanism will allow us to determine how this SNP alters function as well as providing potential new avenues for anti-viral drug and vaccination strategies.