Helmholtz University Junior Research Group 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.

Contact

Dr. Guoliang Cui
T Cell Metabolism (D140)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 1370

Selected Publications

  • Cui, G., Staron, Matthew M., Gray, Simon M., Ho, P.-C., Amezquita, Robert A., Wu, J., and Kaech, Susan M. (2015). IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity. Cell 161, 750-761.
  • Cui, G., Qin, X., Wu, L., Zhang, Y., Sheng, X., Yu, Q., Sheng, H., Xi, B., Zhang, J.Z., and Zang, Y.Q. (2011). Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J Clin Invest 121, 658-670.
  • Cui, G., Qin, X., Zhang, Y., Gong, Z., Ge, B., and Zang, Y.Q. (2009). Berberine differentially modulates the activities of ERK, p38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice. J Biol Chem 284, 28420-28429.
  • Jingxia Wu, Sicong Ma, Roger Sandhoff, Yanan Ming, Agnes Hotz-Wagenblatt, Vincent Timmerman, Nathalie Bonello-Palot, Beate Schlotter-Weigel, Michaela Auer-Grumbach, Pavel Seeman, Wolfgang N. Löscher, Markus Reindl, Florian Weiss, Eric Mah, Nina Weisshaar, Alaa Madi, Kerstin Mohr, Tilo Schlimbach, Rubí M.-H. Velasco Cárdenas, Jonas Koeppel, Florian Grünschläger, Lisann Müller, Maren Baumeister, Britta Brügger, Michael Schmitt, Guido Wabnitz, Yvonne Samstag, Guoliang Cui. Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8+ T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness. (2019) Immunity In press.
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