Division of T Cell Metabolism

Cancers affect hundreds of millions of people worldwide. Immune cells, such as T cells, play a very important role in protection against cancer development. However, tumor-infiltrating T cells are frequently immunosuppressed or “exhausted”, which is characterized by expression of immune checkpoint molecules (such as PD-1, TIGIT, LAG-3, etc) and reduction of anti-tumor effector cytokines (such as IFNg, TNFa, etc). Immune checkpoint blockade has achieved huge clinical success in several types of cancers, but only a subset population of cancer patients benefit from it. This suggests that we may be still at the early stage in understanding the immunosuppressive nature of tumor microenvironment. Thus, one of the most important questions in this field is to identify the factors causing T cell exhaustion in the tumor. Our previous findings suggest that metabolites, such as lipids, regulate T cell survival and effector function. Based upon the previous work, our T Cell Metabolism group will use mouse melanoma models to identify the metabolic checkpoints regulating anti-tumor T cell bioenergetics, survival and effector functions.

The long-term research goal of our T Cell Metabolism group is to translate our findings made using the mouse models into clinical benefits. Particularly, we are interested in addressing the following questions: 1) which lipid metabolites regulate human anti-tumor T cell effector function and survival? 2) what is the mechanism underlying lipids-induced T cell immunosuppression and 3) how to enhance human anti-tumor T cell function by regulating the lipid metabolic pathways? These future studies may lead to novel immunotherapies by targeting T cell-intrinsic lipid metabolism.