We invite you to join us online on Thursday, October 19th, from 3:00 PM to 4:00 PM, for a presentation by:

 

Dr Luis Zapata Ortiz –  Evolutionary Immunogenomics Team, Institute of Cancer Research. 

 

“Immune evasion shapes the landscape of driver genes and influences response to immunotherapies.”

 

Cancer is an evolutionary process where sequential accumulation of mutations drive novel phenotypes and hallmarks. One of these phenotypes allows tumor cells to hide from the immune system and therefore accumulate antigens. In this study, we characterize over 10,000 cancer samples to determine the strength of immune selection and the prevalence of immune escape mechanism across tumors. We identified weak signals of selection and widespread immune evasion. When accounting for immune escape status we could identify differences on the selective advantages observed in common cancer genes. Moreover, by analysing a cohort of more than 300 patients that received immunotherapy, we demonstrated that immune selection and escape underlies therapeutic response. This understanding, primarily based on mutation data, offers insights into cancer pathogenesis and the potential influence on immunotherapy response, underscoring the importance of considering immune evasion in therapeutic strategies.

 

Dr Luis Zapata Ortiz leads the Evolutionary Immunogenomics Team at the ICR. His work has focused on developing immunogenomic-based metrics to predict response to immune checkpoint inhibitor therapies. His groundbreaking research, including publications in esteemed journals such as Nature Genetics and Genome Biology, has shed light on the clinical impact of immunoediting and the strength of immune selection.

His academic journey began with a major in Biotechnology Engineering at the University of Chile, a short-stay in University of California in Davis, followed by a Ph.D. in Biomedicine at the Centre for Genomic Regulation in Barcelona. As a Marie Curie Postdoctoral Fellow at the ICR, Luis made significant contributions to understanding how evolution shapes the genome of cells within our bodies, particularly focusing on the impact of the immune system on genetic variability.

 

 &

 

 

Dr Tolga Bozkurt – Department of Life Sciences, Imperial College London.

 

“AI guided discovery of Autophagy modulating virulence factors from infectious agents.”

 

To withstand stressful conditions, eukaryotic cells use a fundamental catabolic process known as autophagy. Autophagy is implicated in various physiological and pathological conditions, particularly in cancer and defence against pathogens, thus directly affecting plant and human health.

Autophagy is regulated through interactions between autophagy modulators and the core autophagy protein ATG8 (LC3/GABARAP in humans). Autophagy modulators contain a crucial sequence called the ATG8 interacting motif (AIM) that facilitates these interactions.

I will discuss our recent breakthrough in using the Alphafold2-Multimer (AF2-multimer) protein modelling pipeline, which accurately identifies both traditional and unconventional AIMs. We've discovered numerous autophagy-modulating effectors in over fifty virus genomes. This discovery promises to deepen our understanding of how viruses manipulate host autophagy, offering new strategies for disease control.

 

Tolga Bozkurt is a reader in Molecular Plant-Microbe Interactions at Imperial College London and the co-founder of the disease resistance biotech startup Resurrect-bio. He has made groundbreaking contributions in understanding how pathogen effectors manipulate membrane trafficking and autophagy to enable infection. TB has pioneered the use of AlphaFold-Multimer for investigating host-pathogen interactions, shedding light on the biology of plant-parasite interactions. His work extends to plant immune receptor networks, employing a targeted bioengineering approach that lays the foundation for Resurrect Bio's pioneering work in the field.

Please note: This webinar is exclusively available to colleagues from the Institute of Cancer Research, the Royal Marsden, Imperial and Imperial College Healthcare.