PhD in Precision Immunology

Supervisor: Dr Carlson Tsui  

Cytotoxic CD8 T cells found in cancer or chronic infection are typically maintained in a dysfunctional state (also known as ‘exhaustion’). T cell exhaustion remains a major mechanism for immune evasion in cancer and represents a significant roadblock for immunotherapies. The recent development of immune checkpoint blockade (ICB), such as PD-1 and CTLA-4 blockade, has shown promising results in reinvigorating exhausted T cells in cancer patients. However, the specific driver cues and signalling axes that dictate therapeutic responsiveness to ICB remains unknown.

We have recently defined a population of precursor of exhausted T cells (T_PEX) with stem-like capacity that resides in secondary lymphoid organs during chronic infection and cancer (Ref 1, 2). These stem-like T_PEX cells are not only crucial to maintain prolonged generation of effector cytotoxic T cells, but also key to mediate the response to ICB. We have further identified specific factors derived from the lymph node microenvironment to be essential in driving their metabolic fitness and therapeutic responsiveness (Ref 3). These findings support the notion that a successful clinical response during ICB is underpinned by specific cell-intrinsic and extrinsic factors.

Our research group aims to define 1) the cell-intrinsic features that dictate stem-like T_PEX cell differentiation and fitness in chronic infection and cancer, 2) the signalling cues and cellular networks that operate within the microenvironment which determine the therapeutic responsiveness of stem-like T_PEX cells, and 3) how we can exploit these cell-intrinsic and extrinsic factors to develop novel immunotherapies.

We are seeking 1-2 PhD students that will take part in addressing some of these questions. We offer a supportive and collaborative research environment, with ample opportunities for training in cutting-edge technologies, including single-cell multi-omics, advanced imaging and spatial analysis, spectral flow cytometry and the use of preclinical models of cancer and chronic infection. You are welcome to contact Dr Carlson Tsui (c.tsui@garvan.org.au) for more details on if you have any questions regarding the project specifics and working at the Garvan.

Reference

1          Tsui C et al. MYB orchestrates T cell exhaustion and response to checkpoint inhibition. Nature 2022. PubMed PMID: 35978192.

2          Wijesinghe SKM et al. Lymph node-derived stem-like but not tumour tissue-resident CD8+ T cells fuel anti-cancer immunity. Nature Immunology 2025. PubMed PMID: 40730900.

3          Tsui C et al. Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade. Nature Immunology 2025. PubMed PMID: 40954251.