For this issue of IMMpress Magazine on Canadian Immunology, we take our readers to April 2024 when immunologists across Canada gathered at scenic Banff, Alberta for the annual spring conference hosted by the Canadian Society for Immunology (CSI). Home to nine CSI spring conferences since 1997, the snow-capped Rockies were the backdrop for four days of scientific and social events.
KEYNOTE
CSI 2024 opened with a keynote address from Professor Dame Fiona Powrie (Univ. of Oxford). She emphasized the use of novel technology in therapeutic discovery, discussed in the context of inflammatory bowel disease (IBD). Powrie and her group leverages a novel technique known as NICHE-seq on regulatory T cells (Tregs) in a mouse model of intestinal colitis. This technique labels photoactivatable T cells upon excitation with near-infrared light. Spatial locations of cells can then be inferred based upon their photoactivation status. Using NICHE-seq, Powrie identified the disruption of Treg compartmentalization during colitis induction, thereby implicating several molecular pathways in the development of IBD pathology in their mouse model. Powrie argues that such novel techniques can provided the needed resolution in heterogenous diseases such as IBD. The proper stratification of large spectra of pathologies permits the identification of underlying molecular drivers to create targeted treatments for IBD.
IMMUNE MECHANISMS IN TISSUE
The first series of talks discussed how local environment influences immune responses. Dr. Adrian Liston (Churchill College Cambridge) proposed a “pan-tissue” model to describe the development of transient tissue-resident Tregs. In this model, circulating Tregs that enter tissue express genes associated with general tissue residency but remain capable of rehoming to most other tissue sites. Dr. Lisa Osborne (Univ. of British Columbia) shared how intestinal helminth colonization improves disease outcomes in a mouse model of multiple sclerosis through intestinal induction and mobilization of protective type 2 immune responses to the brain. Dr. Gretchen Diehl (Memorial Sloan Kettering Cancer Center) demonstrated that microbiota exposure in early life supports the development of anti-microbial effector T cells that cross-react against other gut microbes in adulthood. Dr. Markus Geuking (Univ. of Calgary) unified concepts from Drs. Liston and Diehl’s talks by showing that microbiota-specific intestinal Tregs that develop in early life can protect against a chemically induced mouse model of colitis. Finally, Dr. Sebastien Talbot (Queen’s University) dipped into the realm of cancer immunosurveillance to examine how sensory neurons that detect pain releases neurochemicals that restrain the anti-tumour function of CD8+ T cells and dendritic cells.
CELL DEATH
The second day of the conference began bright and early with Dr. Douglas Green (St. Jude Children’s Research Hospital) explaining how sleep interruption can render a sublethal lipopolysaccharide challenge fatal in otherwise healthy mice because of increased wakefulness. This wakefulness causes neuronal activity that pathologically activates macrophages in the brain. Next, Dr. Kim Newton (Genentech) described to us how the interferon regulator factor members IRF1 and IRF2 modulate inflammation and pyroptotic cell death by influencing chromatin remodeling. Dr. Barbara Porto (Univ. of Manitoba) introduced necroptosis as an alternate flavour of cell death that can exacerbate lung pathology after respiratory viral infection through an autocrine tumour necrosis factor axis. Dr. Shawn Beug (Univ. of Ottawa) brought a translational perspective using a family of drugs called SMAC mimetics that inhibit apoptosis proteins and showed how they can enhance multiple aspects of the anti-tumour immune response. Lastly, Dr. Simona Stäger (Institut national de la recherche scientifique) described how chronic human immunodeficiency virus (HIV) infection sensitizes CD4+ T cells to multiple routes of apoptosis through a TLR7-IRF5 axis.
NON-INVASIVE IMMUNE CELL IMAGING
The final symposium focused on visualization of immune cells to complement existing clinical therapies. Dr. Charles Truillet (Univ. Paris-Saclay) discussed the use of radioisotope-labelled antibodies combined with positron emission tomography (PET) imaging to optimize cancer treatments. One example would be to track infiltration of anti-tumour CD8+ T cells after treatment with immune checkpoint blockade. Dr. Israt Alam (Stanford University) expanded on Dr. Truillet’s talk by giving examples of T cell PET tracers in current clinical trials and additional PET tracer candidates for cancer immunotherapy monitoring. The final talk of the conference was given by Dr. John Ronald (Western University), who spoke about incorporation of PET imaging reporters into chimeric antigen receptor-based cell therapies to help accelerate preclinical development and allow a better understanding of how these engineered cells behave once given to patients.
AWARDS AND ACKNOWLEDGEMENTS
This year, the prestigious Bernhard Cinader Award was bestowed to Dr. Fumio Takei (Univ. of British Columbia, Terry Fox Laboratory). Dr. Takei discussed his career working on innate lymphoid cells (ILCs), from his initial discovery of the first known natural killer (NK) cell receptor family Ly49, to his current interest on ILC2s. Although lacking in antigen-specificity, lung ILC2s exhibit a lymphocyte-like activation response involving an expansion and contraction phase. Like lymphocytes, these primed ILC2s develop a memory-like capacity with enhanced effector function upon reactivation. Activated lung ILC2s may also migrate to other tissue sites such as the liver and play a protective role in a model of liver fibrosis. Aside from his scientific accomplishments, Dr. Takei also shared with us the importance of collaboration and perseverance, citing Nobel laureates and giants in the field of biochemistry Drs. Cesar Milstein and Frederick Sanger as major figures in helping to shape his academic career. Dr. Takei emphasized the advocation of your own work; he recalled with great humour the rejection of Dr. Sanger’s pioneering work in DNA sequencing by the journal Nature as “[a technique of] no biological significance”, which later won Dr. Sanger the 1980 Nobel Prize in Chemistry.
This was a phenomenal year for the local immunology community at the University of Toronto as we offer our warmest congratulations to Dr. David Brooks and Dr. Sarah Crome, recipients of the Investigator Award and New Investigator Award, respectively, as well as all travel and poster award winners.
The annual CSI meeting is an enormous undertaking that is only made possible by the tremendous efforts of the local organizing committee, trainee engagement committee, staff, and generous support from sponsors. A big thank you to the local organizing committee from the Univ. of Alberta and Univ. of Calgary: Drs. Troy Baldwin (Chair), Colin Anderson, Xavier Clemente-Casares, Markus Geuking, Kathy McCoy, and Sue Tsai; and to this year’s CSI sponsors: BioLegend, Miltenyi Biotec, Beckman Coulter, Cytek Biosciences, Li Ka Shing Institute of Virology (University of Alberta), Olink, the International Microbiome Centre (University of Calgary), Mucosal Immunology, BD Biosciences, Sony, CIHR – Institute of Infection and Immunity, University of Toronto, CIHR – Institute of Gender and Health, and Pathogens and Immunity.
Congratulations on another successful conference and we look forward to seeing everyone again next year in Gatineau, Quebec for the 37th CSI meeting!
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