This past April, immunologists from across Canada gathered with fervour at the 29th Annual Conference of the Canadian Society for Immunology (CSI) in Ottawa to discuss frontiers in the field. IMMpress Magazine was there to review the science, scenery, and progress of student professional development workshops.
DAY 1: Keynote
The meeting opened with a keynote address from Dr. Arlene Sharpe (Harvard Medical School). Dr. Sharpe has shown a role for the inhibitory molecules PD-1 and CTLA-4 in limiting T follicular helper (Tfh) and T follicular regulatory (Tfr) cell differentiation and function. However, it is not the absolute numbers but rather the ratio of Tfh to Tfr cells that determines antibody production in vivo; therefore, it is the context of the response with its collective signals that will determine this balance. Dr. Sharpe’s lab is currently investigating the mechanism by which Tfr cells mediate suppression of antibody responses for a better understanding of immunoregulation in germinal centres. This work opens the door to exciting new immunotherapy targets using PD-1 combination therapy.
DAY 2: Myeloid Cells and Immunity – The Good, The Bad, and The Ugly
The first symposium of the conference illuminated both the protective and the damaging outcomes of innate immune responses. In the realm of neutrophils, Dr. Ronald Germain (National Institute of Allergy and Infectious Diseases, NIH) presented impressive microscopy imaging and tracking studies of neutrophil migration. His lab showed that neutrophil swarming at the site of damage in turn recruits the monocytes required for controlling the dissemination of bacteria. Dr. Paul Kubes (University of Calgary) noted that neutrophils eventually disappear from the wound site, re-enter the circulation, and return to the non-injured peripheral tissue (coined “vacation spots”) within 24 hours. He also demonstrated that the monocytes layered above the injury site are derived from the peritoneum. Macrophage development was addressed further by Dr. Slava Epelman (University Health Network, University of Toronto). Dr. Epelman identified embryonic-derived macrophages that promote angiogenesis and other repair functions, thus suggesting that targeting subtypes based on origin may have therapeutic value in the future.
On the other hand, targeting systemic myeloid cells may be an important strategy in treating β-amyloid associated brain diseases such as Alzheimer’s disease and multiple sclerosis (MS). Dr. Serge Rivest (Université Laval) discussed how monocytes patrol the brain during amyloid diseases and internalize amyloid β before re-entering the circulation. He noted that blood vessels in the brain are crucial to this function.
Finally, Dr. Alan Sher (National Institute of Allergy and Infectious Diseases, NIH) reminded us that working with mice does not always translate into the clinic. His work in Toxoplasma gondii has shown that the live parasite triggers human dendritic cells and monocytes through phagocytic uptake and lysosomal degradation. In contrast, TLR recognition of certain released components is sufficient for immune activation in the murine model but not in humans.
DAY 3: Overcoming Exhaustion in Viral Infection and Cancer
The second symposium explored T cell exhaustion in the context of chronic viral infections and cancer immunotherapy. Dr. David Brooks (University Health Network, University of Toronto) showed that blocking type I interferon (IFN) signalling results in enhanced viral control and rescues Th1 differentiation in persistent lymphocytic choriomeningitis (LCMV) infection. Continuing on the theme of type IFNs, Dr. Dorian McGavern (NIH – NINDS, Division of Intermural Research) discussed the motility paralysis (or “locking down”) of exhausted T cells during persistent LCMV and explained how blocking IFNAR resurrects antibody responses by promoting early CD8 T cell exhaustion and extended retention in the white pulp.
On the cancer side, Dr. Ana Carrizosa Anderson (Harvard Medical School) functionally distinguished subtypes of exhausted tumour infiltrating lymphocytes (TILs) using Tim-3 and PD-1. She also showed that mice deficient for metallothionein zinc chaperons have TILs that do not exhibit functional exhaustion. Dr. Brad Nelson (University of Victoria) introduced PD-L1 as a positive prognostic indicator in high-grade serous carcinoma (HGSC); CD8 TILs are only favourable in HGSC when companion B cell and CD4 T cell responses occur in the tumour. Lastly, Dr. Pamela Ohashi (Princess Margaret Cancer Centre, University of Toronto) discussed how regulatory NK cells have been shown to limit CD8 T cell immunity in persistent LCMV and are also associated with slow growth TILs in cancer immunotherapy. Depletion of these NK cells results in increased TIL expansion and a shift in T cell cytokine profile. Thus, culturing TILs with or without NK cells can affect the efficacy of treatment and patient survival in clinical trials.
DAY 4: B Cells – More Than an Antibody Factory
B cells took the spotlight on the final day of the conference. Dr. Aaron Marshall (University of Manitoba) introduced the idea of targeting B cell metabolism as a strategy for treating autoimmunity. Dr. Amy Johnson (Ohio State University) shifted gears to talk about blocking BCR signalling in the treatment of chronic lymphocytic leukemia (CLL) by targeting Bruton’s tyrosine kinase (Btk) in the PI3K pathway.
In a fascinating examination of B cell tolerance checkpoints, Dr. Eric Meffre (Yale University) showed that while most autoimmune diseases are associated with defective central tolerance of B cells, patients of MS instead have defective peripheral tolerance mechanisms that are associated with impaired Treg function. Dr. Amit Bar-Or (McGill University) highlighted the importance of B cells as antigen-presenting cells in MS: transient B cell depletion treatment by rituximab (anti-CD20) results in B cells returning with a more regulatory cytokine profile, thus leading to decreased proinflammatory activity of T cells during amelioration of disease. Dr. Michael Gold (University of British Columbia) presented additional evidence of B cell activation for antigen presentation. His lab has shown that the GTPase Rap1 functions as a master regulator for actin and microtubule traffic flow and cytoskeleton organization during antigen internalization.
Finally, as B cells are the known antibody factories, Dr. Nicole Baumgarth (University of California) suggested a Blimp1-independent antibody secretion pathway. Knocking out Blimp-1 in murine B cells lead to decreased IgM secretion, which interestingly protected against influenza A and immune pathology. This indicates a requirement for functional B cells in infection models.
A Word from our Sponsors
Gold sponsors BioLegend and Affymetrix eBioscience, and silver sponsors StemCell Technologies Inc. and Miltenyi Biotec gave brief presentations on innovations in magnetic bead assays, RNA isolation, and cell separation methods, among others. A big thank you to all the sponsors!
And the Oscar goes to…
Award winners were celebrated at the annual conference banquet, which took place in the gorgeous totem exhibit at the Canadian Museum of History across the Ottawa River in Gatineau, Quebec. Meeting attendees were treated to dinner in the Grand Hall of the museum surrounded by artistic totem poles of the First Peoples of Canada’s Pacific Coast. Travel awards, which allow many students, post-doctoral fellows, and new investigators to attend the conference, were also presented at the banquet, along with top-notch poster competition winners.
The Cinader Award, presented to a distinguished member of the immunology community for scientific achievement and leadership, was awarded to Dr. Tania Watts (University of Toronto) this year. Dr. Watts gave a retrospective of her career thus far, detailing the evolution of both the science conducted in her lab and herself as a scientist (from her beginnings as a biochemistry undergraduate research student in Alberta). Dr. Gillian Wu (University of Toronto, York University) was the recipient of the John D. Reynolds Award for long-term service to the CSI, while Dr. Jennifer Gommerman (University of Toronto) and Dr. Irah King (McGill University) were presented with the Investigator Award and the New Investigator Award, respectively.
Becoming a Professional
In the last few years, the CSI conference has focused on developing scientific professionals—regardless of whether or not they become academic scientists. With the help of Dr. Nana Lee (University of Toronto) and student volunteers, this year’s conference provided several sessions to help trainees develop their various skills away from the bench.
The sessions opened with Dr. Lee’s “Success After Graduate School” seminar, which addressed the importance of having a career plan during training and continually assessing one’s impact on research Michael Bloom (The Conference Board of Canada, CBC) discussed why the job hunt can be so tedious in the Canadian market. Mr. Bloom is involved in a new CBC research initiative that tracks PhD graduates after their degrees, and has found that graduates face substantial challenges in finding alternative employment, as their skillset is not always understood by employers outside of academia. Hopefully, this work can help bridge the gap between academic training and the real job market.
A new addition to CSI this year was a Trainee Mixer, and event designed to have students mix-and-mingle with industry representatives and scientists. The event was attended by directors, managers, sales representatives, consultants, and associates from various companies as well as academic researchers. Unfortunately, the mixer was a victim of hungry stomachs, as most people left early to look for dinner after the food ran out. It would also have been more helpful if the invited professionals were introduced and better identified so that trainees knew who to approach. However, trainees got a second opportunity to chat with professionals at the careers discussion panel. The panel consisted of an entrepreneur in industry, a science policy director, a regulatory affairs evaluator, a flow cytometry facility manager, an RCMP forensic scientist and an infectious disease clinical researcher. This broad range of panelists gave the students a new perspective on how far their graduate degrees can stretch.
The one-minute thesis (1MT) made a comeback this year (and looks to stay as a conference tradition). Trainees were asked to give a 60-second “elevator pitch” to pique interest for their posters. This provided an entertaining display of creativity ranging from PowerPoint diagrams to hand-drawn cartoons to paper cut-outs. Overall, the 1MT was a challenging exercise for students and postdoctoral fellows in effective and concise communication.
The career development programs at CSI help trainees expand their skills and offers an opportunity to be trained by the best in the business. This has been a fantastic addition to the CSI meetings over the last two years and will continue to help graduate students plan for their future careers in immunology.
In closing, CSI was a great success this year! A big thank you to Lori Coulthurst and the local organizing committee of Dr. Katrina Gee (Queen’s University), Dr. Sam Basta (Queen’s University), Dr. Andrew Makrigiannis (Dalhousie University), Dr. Subash Sad (University of Ottawa) and Dr. Tania Watts (University of Toronto) for a very successful conference. Everyone is looking forward to next year on the slopes in Banff!
Angela Zhou is a 4th year PhD candidate at University of Toronto in the Department of Immunology under the supervision of Dr. Tania Watts.
Carlene Petes is a 4th year PhD candidate at Queen’s University studying Microbiology and Immunology in the Department of Biomedical and Molecular Sciences under the supervision of Dr. Katrina Gee.