SFB 1054 Seminar - Roger Geiger

Title: Metabolic interventions to enhance anti-tumor T cell responses

During the first part, I will present a project in which we analyzed protein synthesis rates and turnover in naïve and activated T cells using mass spectrometry. We found that while the majority of the proteome of resting naïve T cells was stable, a small set of proteins turned over rapidly. Rapid protein turnover enabled rapid tunability of their expression to promote activation and differentiation. Despite low glycolytic and translational rates, naïve T cells contained large numbers of glycolytic enzymes, ribosomes and mRNAs that were rapidly engaged only following stimulation to ramp up the activation program. Collectively, these data reveal a minimal maintenance program in naïve T cells and identify protein turnover, preformed stores of enzymes and an idling translational machinery as key elements that poise T cells for rapid responsiveness.

In the second part, I will present a project in which we analyzed the dynamics of the proteome and metabolome following activation of human naïve T cells. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes in activated T cells and promoted the generation of central memory-like cells that were endowed with a higher survival capacity and, in a mouse model, anti-tumor activity. Oral administration of L-arginine to tumor-bearing mice increased the numbers of tumor-infiltrating T cells and inhibited the growth of tumors synergistically with PD-L1 blockade. Because daily oral administration of high doses of L-arginine is impractical in the clinic, we developed in collaboration with the company Synlogic a non-pathogenic, engineered bacterial strain that produces high levels of L-arginine locally in tumors. Intratumoral administration of L-arginine-producing bacteria synergized with PD-L1 blockade.

Roger Geiger - Website

Venue:

BioMedical Center (BMC), Room N 01.017,
Großhaderner Str. 9, Planegg-Martinsried

Host: Reinhard Obst (B07)

If you wish to talk to the speaker, please contact Katharina Frank