Division of T Cell Metabolism
Dr. Guoliang Cui

B16 mouse melanoma tumor-infiltrating lymphocytes or TILs (left) are
exhausted and express higher levels of inhibitory receptors (such as PD-1 and
Lag-3) than splenic T cells (right). Our research goal is to understand how
metabolism regulates anti-tumor T cell effector function and survival.
© dkfz.de
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.