Ajithkumar Vasanthakumar lab

Tregs are known to suppress anti-tumour immunity, thereby promoting tumour growth. Therapeutic targeting of Tregs is therefore an appealing strategy to enhance anti-tumour immunity. However, systemically blocking Tregs carries the risk of inducing fatal autoimmune side effects, as they play a critical role in preventing autoimmunity. Our goal is to identify mechanisms to selectively deplete Tregs within tumours or tumour-bearing tissues, thereby boosting anti-tumour immunity while minimising side effects.

Cellular metabolism is critical for the differentiation, growth and function of tumour cells and immune cells. Metabolic intermediates serve as catalysts for several cellular processes including gene transcription. Systemic metabolic changes also influence anti-tumour immune responses and immunotherapy outcomes. We aim to understand how cellular metabolism and tumour derived ‘oncometabolites’ shape the transcriptional landscape of tumour infiltrating immune cells. We also investigate how changes in systemic metabolism affects anti-tumour immunity and immunotherapy outcomes.

The majority of Tregs develop in the thymus and subsequently migrate to secondary lymphoid and non-lymphoid tissues. To populate various organs and perform a wide range of immune and non-immune functions, Tregs undergo further differentiation in the periphery to become effector Tregs. We investigate the transcriptional and metabolic mechanisms underlying this differentiation process to gain a deeper understanding of the seeding and maintenance of Tregs in tissues and tumours.

Tregs are known to perform multiple non-immune functions, including tissue repair and the regulation of systemic metabolism. We are particularly interested in understanding Treg function in metabolic organs, such as the gut, liver, and adipose tissue. In these organs, we investigate the cellular interactions between Tregs and other non-immune cells, including stromal cells and neurons, to better understand the role of Tregs in tissue homeostasis and physiology.