CSI 2022

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 17-20th. 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.

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Keynote

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 resulting 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.

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Anti-Tumor Immunity

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 PD-1 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 (McGill University) 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.

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Layered Immunity

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 with 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.

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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.

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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!