“Systems analyses of anti-tumour T cell responses”

Host: Dr Henry McSorley Dr Andy Howden & Dr Linda Sinclair  

Venue: The Murray Room CTIR 2.84 

Biosketch 

Roger Geiger obtained his Master’s and PhD degrees from ETH Zürich. During his PhD studies with Ari Helenius, Roger investigated how non-enveloped viruses penetrate the host cell membrane. He then joined the laboratory of Antonio Lanzavecchia at the Institute for Research in Biomedicine (IRB) to study metabolic regulations of T cell responses. In 2016, Roger joined the research group of Matthias Mann at the Max Planck Institute of Biochemistry in Munich and received training in mass spectrometry-based proteomics. In 2017, Roger started his research group at the IRB focusing on immune responses to tumours using systems biology approaches. 

Abstract 

I look forward to presenting an overview of our research. In the first segment of my talk, I will present a study on the capability of naïve T cells to rapidly respond to antigens. Utilizing a mass spectrometry-based pulsed SILAC approach, we assessed protein synthesis rates in primary human T cells and estimated mRNA copy numbers through RNA-Seq data. This integrative analysis unveiled that resting T cells maintain ready-to-act molecular machinery, such as idle ribosomes and inactive glycolytic enzymes, allowing a swift response to external stimuli. 

The second part of my presentation will focus on our investigation into the potentiation of anti-tumour T cell responses via L-arginine. We discovered that oral administration of L-arginine increased the number of tumour-infiltrating T cells, acting synergistically with PD-L1 blockade to induce tumour regression. Due to practical limitations with high-dose L-arginine administration, we developed a novel approach: an engineered probiotic bacterium capable of converting ammonia—a common metabolic waste product in tumours—into L-arginine. This strategy led to remarkable synergistic effects with PD-L1 blockade in tumour clearance, highlighting the potential of therapeutic bacteria in modulating tumour metabolism to boost anti-tumour immunity. 

In the final section, I will discuss a project in which we analyzed proteomes of immune cells isolated from tumours of HCC patients. We discovered that chronically stimulated T cells in tumours upregulate the protein AFAP1L2. Genetic ablation of Afap1l2 in murine T cells enhanced their anti-tumour activity in preclinical tumour models