After a two-year hiatus of in-person conferences, the 34th annual Canadian Society for Immunology (CSI) meeting reunited immunologists in the port city of the Canadian Atlantic, Halifax, Nova Scotia, on June 1720th. Situated at the beautiful Marriott Harbourfront Hotel, the three-day conference was packed full with discussions of exciting and novel research, workshops, and a chance for trainees to present their own work. We want to thank the local organizing committee chair Dr. Andrew Makrigiannis from Dalhousie University and his team for the incredible and safe in-person conference.
The conference started off with keynote speaker Dr. Anjana Rao (La Jolla Institute for Immunology) who shared her insight into how pathways regulating methylation and demethylation impacted oncogenesis. Dr. Rao and her team found that across multiple cell types that included T cells, regulatory T cells, and myeloid cells, loss-of-function of the TET dioxygenase family—enzymes notable for their role in DNA demethylation—altered methylation signatures to promote aberrant cell lineage specification and cancer development.
However, under the right contexts, TET deficiency can also prove beneficial for cancer patients. One such scenario involved an individual undergoing chimeric antigen receptor (CAR) T cell immunotherapy to treat an advanced form of chronic lymphocytic leukemia, where insertion of the CAR transgene led to the disruption of one of the TET2 alleles. Serendipitously, this patient already harbored a loss-of-function mutation within the second allele, ablating TET2 activity within the CAR T cells and resulted in anti-tumor activity accompanied by complete remission. Dr. Rao’s lab found that the altered methylation patterns caused by TET2 dysfunction impacted the differentiation state of the CAR T cells and their proliferative capacity, resulting in a lifesaving therapeutic outcome. This work showcased the potential in targeting the epigenome and the clinical significance that is achievable when we understand the molecular mechanisms.
The conference’s first symposium focused on both the pro and anti-tumorigenic immune responses to cancer. Dr. David Brooks, (University of Toronto) who served as a co-chair, began by discussing the dichotomy of how Type I interferons (IFNI) can drive proinflammatory responses in immune cells but are suppressive for cancer cells. He showed that immune cells, notably T cells, responded differently to IFN-I due to variations in chromatin accessibility signatures and that these variations could predict the success of PD1 blocking immunotherapy. Dr. Thornsten Mempel (Massachusetts General Hospital) then spoke about the cellular interactions within the tumor microenvironment that regulate T cell function. He showed how two distinct trajectories of tumor-infiltrating regulatory T cells initiated IFNγ expression, correlating the degree of expression to the success of checkpoint inhibitor therapy response.
Dr. Brent Johnston (Dalhousie University) continued the discussion by showcasing the therapeutic potential of natural killer T cell (NKT) activation in immunotherapy. He spoke on how NKT cells can work in combination with oncolytic virotherapy and checkpoint inhibitor therapy to enhance therapeutic outcomes. Lastly, Dr. Daniela Quail concluded the session by talking about the inflammation and cancer metastasis associated with obesity, finding that obesity led to neutrophil accumulation in metastatic sites, burdened the surrounding tissue, and allowed for increased access to tumor cells.
The second symposium focused on immune system development and layered immunity. Co-chair Dr. Padmaja Subbarao (University of Toronto) began by discussing her work on characterizing the trajectory of infant asthma and allergy development. She showcased how the power of deep datasets and machine learning can provide insights into the heterogeneity of childhood asthma and can lead to improved diagnostics and therapeutics. She also discussed how the microbiome can influence immune system development, mediating the development of traits associated to asthma progression. Next, Dr. Petter Brodin (Imperial College London & Karolinska Institute) presented his work on how the immune system evolves early in life along with the microbiome. He spoke on the sensitive interplay between commensal bacteria and immune cell profiles of newborns, showing that pregnancy length influenced the epigenetic signatures and compositions of immune cells towards that of tolerance or resistance against commensal bacteria.
Dr. Ana Cvejic (University of Cambridge) continued the discussion with a talk on human fetal blood development at a single-cell level. She presented the impact of the epigenetic landscape on hematopoietic stem cells and multipotent progenitor differentiation, showing the importance that DNA motif accessibility has on cell fate choice, and identifying the patterns of transcriptional accessibility that influence erythroid or myeloid/lymphoid lineage differentiation. Dr. James E. Gern (University of Wisconsin) then spoke about the approaches used to understand childhood asthma at a population level. He described that the conclusions drawn from single cohorts of data is complicated when compared to different populations from varying environments. Instead, using a collaborative approach containing multiple cohorts, he collected powerful datasets from an extensive population across the United States to find that race, socioeconomic factors, and genetic polymorphisms all contribute to an increased risk of asthma development. Finally, co-chair Dr. Kathy McCoy (University of Calgary) spoke about how the maternal microbiome can influence the development of the neonatal immune system. She described that the susceptibility of children to childhood illnesses including neurodevelopmental disorders and asthma is correlated to the microbiome transmitted from the mother during birth.
Primary Immune Deficiencies
The third and final symposium of CSI looked into primary immune deficiencies and the dysregulation and inflammation associated with developmental defects in the thymus. Dr. Georg Holländer (University of Oxford) began the symposium by sharing his work on key timings of thymic development and how molecular defects can affect it, observing that the mouse and human thymus have very different developmental windows. By creating a Δ550 variant of the FOXN1 transcriptional factor, his group highlighted the importance of FOXN1 on transcription, with the defect leading to its reduced activity and localization, culminating in the abrogation of proper thymus development. Dr. Liana Falcone (University of Montreal & IRCM) then highlighted the role of the microbiome in causing inborn errors of immunity, specifically in Chronic Granulomatous Disease (CGD). Using CGD mouse models, her lab found that colitis susceptibility is influenced by the microbial signature established at birth.
The co-chair of the seminar, Dr. Hélène Decaluwe (University of Montreal) discussed T cell exhaustion and the immeasurable value of clinical work studying patients as a way to better understand the immune system and immunodeficiencies. In severe combined immunodeficiency (SCID) patients for example, CD4 T cell abundance influenced the degree of T cell exhaustion post-transplantation, allowing the group to use exhaustion scores as a biomarker for T-cell reconstitution in future transplantation therapies. Next, Dr. Aleixo Muise (University of Toronto) showcased how studying extreme phenotypes in patients with Inflammatory Bowel Disease (IBD) can identify underlying genetic problems and provide insights into human biology. He found that certain patients who possessed gain-of-function mutations within the Spleen Tyrosine Kinase gene had immune dysregulation and inflammation, allowing his group to develop novel treatment options for IBD patients. Finally, the co-chair Dr. Stuart Turvey (University of British Columbia) reported on a new human immune deficiency. He presented that complete deficiencies in the NFAT family of transcription factors of activated T cells, specifically NFAT1, impacted joint contractures, osteochondromas, and B cell malignancy.
Awards & Acknowledgements
Congratulations to Dr. Brad Nelson (BC Cancer, University of Victoria & University of British Columbia) for receiving the Bernhard Cinader Award to honor his brilliant scientific contributions and his leadership within the immunology community. The John D. Reynolds Award was received by our own Dr. Juan Carlos Zúñiga-Pflücker (University of Toronto) for his continued service and excellence to the CSI.
The Investigator Award was given to Dr. Kathy McCoy (University of Calgary), the New Investigator Award was given to Dr. Matthew Macauley (University of Alberta), and the New Investigator Travel Awards were received by Dr. Deanna Santer (University of Manitoba), Dr. Jean-Francois Lauzon-Joset (University of Laval), and another of our own, Dr. Matthew Beuchler (University of Toronto). Additionally, cheers and congratulations to all travel and poster award winners this year!
We would like to thank all who generously donated and the CSI 2022 sponsors: Platinum sponsor – BD Biosciences; Gold sponsor – Biolegend; Silver sponsors – 10X GENOMICS, Cytek, Miltenyi Biotec, and STEMCELL Technologies; Bronze sponsors: Adaptive Biotechnologies, Luminex, and Qiagen; Cinader Award Sponsor – Akoya Biosciences; Educational Sponsor – CIHR Institute of Infection and Immunity; General sponsors – Cedarlane, Journal of Leukocyte Biology, Kyowa Kirin, Lumicks, and Paraza Pharma Inc.
Finally, we thank the organizers, staff, and sponsors for making the 34th CSI meeting possible. A huge thank you goes out to the local organizing committee from Dalhousie University and Memorial University including Dr. Andrew Makrigiannis (Chair), Dr. Jeanette Boudreau, Dr. Sherri Christian, Dr. Francesca Di Cara, Dr. Thomas Issekutz, Dr. Brent Johnston, Dr. Jean Marshall, Dr. Channakeshava Sokke Umeshappa, and Dr. Jun Wang.
Congratulations for the huge success on a long-awaited, in-person CSI conference!
See you next year in Orford, Quebec for CSI 2023!
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