The Cytokine Society is committed to supporting the next generation of scientists — not just through world-class programming, but by opening our community’s doors to emerging researchers early in their careers. At Cytokines 2025 in Seattle (November 2–5), we were pleased to welcome a cohort of postbaccalaureate scholars from PROPEL Northwest, a University of Washington-based program that provides research experience and graduate school preparation for trainees committed to advancing science and building community in the Pacific Northwest.
We invited the PROPEL scholars to do what scientists do: observe, synthesize, and communicate. Each student was asked to select a session or talk that captured their interest and write a concise summary for our broader membership. The results speak for themselves — these are thoughtful, engaged accounts from scientists at the beginning of what we hope will be long and productive careers.
- Ada De La Cruz,
- Olivia Dong
- Christina Gao
- Kira Hoffman
- Aletta Li
- Dylan Omelia
- Charlie Rezanka
Kira Hoffman: Symposium 12 – The Role of Cytokines in Cancer
Though I enjoyed all of the symposiums that I attended at Cytokines, I was particularly intrigued by symposium 12 focused on the role of cytokines in cancer. In the first presentation of the symposium, Dr. Brendan Jenkins from the University of Adelaide spoke about the preferential requirement for IL-18 in inflammasome-driven upper gastrointestinal cancers.
It has long been understood that inflammasomes play a key role in regulating innate immunity in inflammatory and autoimmune disease, but until recently, their role in inflammation-associated tumorigenesis was not well established or understood. In this study, it was found that the inflammasome adaptor apoptosis-related speck-like protein containing a CARD (ASC) and its effector cytokine IL-18 play an important role in promoting the formation of GI cancers, and that ablating or blocking them leads to suppression of tumor growth.
The ASC/IL-18 signaling axis was found to promote the formation of cancerous GI tumors by suppressing normal apoptosis of GI cancer cells by an IL-18 mediated inflammation-independent mechanism, and it was demonstrated that knocking out IL-18 led to suppressed formation of GI tumors in vivo. Additionally, it was found that IL-18 was preferentially used by inflammasomes over its relative IL-1B in gastric cancer models.
These findings were elucidated using a mouse model of pancreatic ductal adenocarcinoma (PDAC), in which upregulated expression and activation of inflammasome components such as ASC, PYCARD (the gene that encodes ASC), and caspase1 are characteristic. When ASC was ablated in PDAC mice, the PDAC phenotype was rescued, and formation of more severe undifferentiated lesions was either delayed or prevented entirely. Ablation of ASC in the mouse model led to reduced expression of mature IL-18, but no change in the expression of mature IL-1B, and IL-18 was found to be the only factor whose expression levels correlated with prognosis in multiple cohorts. Cohorts with high IL-18 consistently had worse prognoses and more prolific tumor growth, while those with lower levels of IL-18 tended to progress much slower and fare better overall.
Armed with the finding that knockout of ASC and IL-18 improve outcomes in pancreatic cancer, Jenkins and his collaborators decided to explore the possibility of ASC-blocking nanobodies as a potential therapeutic treatment. Nanobodies are a type of single-domain antibody fragment derived from monomeric heavy chain antibodies found in camelid species. They are very small, very stable, have high affinity and specificity for their antigenic target, and relatively low immunogenicity. All of these factors combine to make nanobodies extremely promising tools for targeting cancers that fail to respond to other existing treatments. The nanobodies developed for blocking ASC worked well in initial testing and were shown to suppress tumor growth significantly.
I found this talk particularly interesting because upper-GI cancers like pancreatic cancer are so notoriously deadly and difficult to treat, so it feels like quite a breakthrough to not only have a parameter that can inform us about a patient’s prognosis, but also to have uncovered a promising new therapeutic target. Learning about nanobodies for the first time was also fascinating, and I am curious to see if we can successfully treat other diseases and cancers with different antigen-specific nanobodies.
I learned and gained so much from attending Cytokines this year. I really enjoyed getting the chance to talk with so many different people about their projects, and to learn about such an incredibly diverse range of topics (from things like aquaculture and the health of farmed fish to clinical studies of human disease and machine learning algorithms). I feel so fortunate to have had the opportunity to attend, and I look forward to next year!
Olivia Dong: Dr. Russell Vance’s talk, “Effector Triggered Immunity of Myxoma Virus”
At the 2025 Cytokines Conference I attended Dr. Russell Vance’s talk on ‘Effector Triggered Immunity of Myxoma Virus’. Dr. Vance is a professor at UC Berkeley and a previous mentor for my current PI, Dr. Patrick Mitchell. As a postbaccalaureate scientist in the Mitchell lab, I have learned about effector triggered immunity (ETI) and the role host immune activators like inflammasomes, play in ETI. I was excited to attend Dr. Vance’s talk to learn more about how his current ETI research relates to the work happening in the Mitchell Lab.
Historically, innate immune research has focused on how an infected host cell recognizes a pathogen by pathogen-associated molecular patterns (PAMPs). To bypass host cell recognition, pathogens release effector molecules which are virulence factors that promote pathogen survival and replication. However, the host cell has evolved mechanisms to recognize these effectors or the downstream signaling events triggered by these effectors, to activate an immune response. This effector triggered immunity has been well-studied in plants but its role in mammalian infections is not well understood. Although several ETI pathways have been characterized in mammalian cells, if and how the mammalian cell relies on these pathways to trigger innate immune activation is unknown. This motivated the Vance Lab to ask: Can we systematically look for ETI in animals?
Their screen identified a viral effector protein, M3.1, that activates host NF-κB, which induces the expression of pro- inflammatory genes including cytokines. Since NF-κB is typically kept inactive by host inhibitors until an immune response is needed, they hypothesized that M3.1 inhibits a host inhibitor of NF-κB, inadvertently activating the host-immune response. To distinguish which host inhibitor M3.1 may be targeting, they performed immunoprecipitation and mass spectrometry to see what M3.1 interacts with inside the cell. One of the major hits was for Zinc finger anti-viral protein (ZAP). ZAP cofactors also came out of the interactome including NYN domain ribonucleases KHNYN, N4BP1, and ZC3H12A. Interestingly N4BP1 and ZC3H12A are known inhibitors of NF-κB.
From this data, Dr. Vance suggested that the viral M3.1 inhibits the mammalian host anti-viral protein ZAP, but in doing so, it also inhibited these NYN proteins thereby unleashing NF-κB and inducing an immune response. NYN proteins are dual function serving as both anti-viral cofactors and negative regulators of host immune response. This ETI mechanism where an inhibitor of the host immune system is targeted by a pathogen leading to activation of host defenses may be a common system, but further investigations are required to understand how prevalent these ETI pathways are among other animals. I found this discovery to be an interesting example of the host-pathogen evolutionary arms race. Viruses may have previously found success with directly inhibiting the host immune system, but in response the host has developed an indirect sensing mechanism in which negative regulators act as sensors to get around viral inhibition of defense. This is similar to my independent research project in Dr. Mitchell’s lab where I am characterizing a new inflammasome pathway that may respond to viral replication compartments. This indicates another example where the host works around viral evasion supporting that ETI pathways in animals may be more common than previously thought.
I’d like to thank the PROPEL NW program for supporting me at this conference and providing the opportunity to network and present my research to colleagues in the field. This was my first international conference, and I had an amazing time learning more about the immune system and feeling part of the global scientific community. I particularly enjoyed presenting at the poster sessions and the Nite Wave band show during the gala!
Dylan Omelia: Ryan Langlois’ talk, “Deciphering how viruses navigate host species barriers using a fibroblast zoo”
I am grateful for the opportunity to attend the International Cytokine and Interferon Society’s annual conference, Cytokines in Seattle, earlier this November. This amazing chance to attend some fascinating and interesting talks was sponsored in order to support post-baccalaureate in PROPEL NW at the University of Washington. The conference was fantastic and it allowed me to expand my knowledge of cytokines and their interactions within the immune system. With each talk, I got to learn more about cytokines as well as how each speaker thinks about each of their vital questions and how they can answer them. That was my favorite part of the entire conference was understanding each person’s different way of thinking through the talks and when talking to them one on one.
One of the most interesting talks that I was able to attend was Ryan Langlois’ talk “ Deciphering how viruses navigate host species barriers using a fibroblast zoo”. With the increased rate of climate change, it results in new interactions of species in high biodiversity regions. As a result of this, the question becomes whether these new interactions result in higher cross species infectivity of viruses in their specific carriers. Because of this, described in Ryan Langlois talk, he proposed the question whether an increase of cross species interactions results in interactions of different viral pathogens. To answer this question, his lab has collected different fibroblasts from a variety of species across Minnesota as well as the world as he coined the term “fibroblast zoo.” With this collection of animal fibroblasts, his lab conducted a screen where they stimulated the fibroblasts with an universal interferon and then infected with viruses with different hosts. This screen hoped to answer whether there were any cross species barriers that demonstrate a change in viral infectivity.
Another talk that I found interesting was Russell Vance’s talk on effector triggered immunity. During the initial infection of pathogens, the immune system has several mechanisms that allow for the body to recognize PAMPS to trigger the innate immune response. However, viruses and other pathogens have evolved to evade these pattern recognition receptors in order to remain invisible to the immune system. As a result, Vance proposed another type of pattern recognition that the immune system employs which recognizes pathogenic proteins rather than pathogen patterns. Vance demonstrates this through Myxoma virus, which is a DNA virus that is within the same family of Smallpox and Monkeypox. The strain that the Vance Lab uses genetically encodes various amounts of effector proteins to demonstrate effector protein function in immune surveillance. M3.1 also acts as a proviral factor for Myxoma virus but interestingly M3.1 also activates NF-kB. In so, the question that the Vance Lab wanted to answer is how can a proviral effector protein initiate an antiviral immune response. As a result, the lab discovered an interaction of negative regulation of NF-kB. M3.1 inhibits a common Interferon stimulation gene, ZAP, which is antiviral against DNA viruses demonstrated through Immunoprecipitation assays and Mass spectrometry as Zap associated proteins are present during myxoma infection. However, ZAP is a negative regulator of NF-kB so during myxoma infection, NF-kB would be unregulated in this mechanism.
Charlie Rezanka: Symposium 6 – Nucleic Acid Sensing
Nucleic acid sensing is a crucial component of the innate immune response. In addition to other sensors, hosts have evolved mechanisms to recognize non-self DNA via the cGAS-STING axis, and RNA through RIG-I-like Receptors (RLR): RIG-I, MDA5, and LGB2. The latter RLR is of particular interest as its function has yet to be elucidated, though both positive and negative regulatory roles of the innate antiviral response have been proposed, despite LGB2 lacking any conventional signaling domains. Consistent with this speculation, Dr. Kurt Horvath’s lab, from Northwestern University, has demonstrated that LGB2 does indeed serve as a negative and positive regulator of its RLR siblings. His research has found that LGB2 helps catalyze the early formation of MDA5 filaments, a crucial oligomer formed when MDA5 is binding to viral RNA. Yet LGB2 can also inhibit RLR signaling, as overexpression prevents larger MDA5 filaments from being formed, leading to an overabundance of small oligomers that do not lead to productive Interferon (IFN) signaling. Likewise, LGB2 was found to interact with RIG-I only in an inhibitory fashion, via suppression of TRAF activation. These findings are the most comprehensive catalogue of LGB2 activity to date, and highlight its role in regulating viral recognition, and subsequent cytokine signaling.
Several additional talks centered around the study of RLRs, particularly on their interactions independent of classical mRNA recognition. Helene Minyi-Yu, of Taiwan’s National University, has done extensive work studying non-coding RNAs from Interferon-stimulated-genes (ISGs). Her lab has found that non-coding ISG RNAs are recognized by MDA5, which in turn promotes further interferon signaling and ISG expression. Furthermore, she has found that long non-coding RNAs (lnc-RNAs) bind to and promote MDA5 dimerization. These lnc-RNAs lack a 5’ cap and rely on a non-canonical translocation mechanism to reach the cytoplasm that is dependent on m5c modification. Minyu-Yu’s findings are consistent with data from patients suffering from systemic lupus erythematosus (SLE), who show high cytosolic levels of m5c and lnc-RNA, suggesting a link between chronic inflammatory conditions and lnc-RNA-driven MDA5 signaling. Nandan Gokhale has likewise done extensive work elucidating a scaffolding role for RNA in promoting MAVS activity. His lab has shown that the disordered region in MAVS is required for MDA5-independent interactions between RNA and MAVS; such binding promotes MAVS signaling by facilitating interactions with downstream adaptors. Interestingly, several RNAs shown to interact with MAVS come from ISGs, providing additional evidence of a catalytic role ISG RNAs play in promoting IFN signaling and further ISG expression.
In addition to the exploration of RNA-sensing, multiple talks from this session discussed STING-driven pathology and how best to manage it. Of these, Martin Jakobsen and his team presented a compelling novel STING agonist called SP2C/H. Current STING agonists have shown poor efficiency in primary human cells, however, SP2C/H was shown to potently degrade STING without activating the protein. This ligand retains sensitivity to 3D-ligase and proteosome activity and is yet to demonstrate any cytotoxicity or off target effects. Jakobsen happily reports that they are heading to clinical trials with SP2C/H.
The Cytokines conference was a novel and profound experience for my scientific training. Having the opportunity to share my research and gather input from peers in my field was an extremely useful and rewarding experience. My current research studies neuronal mechanisms of resistance to necroptotic cell death. As there are few neuroimmunology researchers in my department, I received substantially more input and interest at the Cytokines poster session than at previous poster opportunities. This feedback was invaluable, helping me develop a roadmap and future directions for my existing work. The experiments and scientific conversations these ideas have fostered are so nuanced that I have even incorporated them into my graduate program applications, as a testament to the caliber of science I have been able to achieve. I’m so grateful to have had the opportunity to contribute to a and diverse and supportive scientific conversation. It has been a pleasure, and an experience I can’t wait to repeat.
Aletta Li: Nathaniel West’s talk on the role of IL-27 on CD8+ T cell-mediated anti-tumor immunity
As a young researcher at the start of my career, I am grateful to have attended the 2025 ICIS meeting, my first academic conference, alongside my PROPEL cohort. This experience further solidified my interest in pursuing research as my lifelong career. I gained invaluable insights into ongoing cytokine research from the scientific sessions and poster presentations. Additionally, through engaging with presenters like Dr. Nathaniel West and receiving constructive feedback for my project, which I presented as a poster, I was able to sharpen my scientific thinking. Although short, I connected with multiple attendees from different backgrounds during the four days at the meeting, many of whom extended their good wishes for my future career. I will cherish my memory at Cytokines 2025 dearly as I move on to the next stages of my scientific journey.
Ada de la Cruz: CNS Hypo-inflammation Drives Mortality in HIV-Associated Tuberculous Meningitis by Dr. Tyler Bold
Mycobacterium tuberculosis (Mtb) remains the world’s leading cause of death from a single infectious agent, responsible for 1.23 million deaths in 2024 according to the World Health Organization. Despite this burden, pathogen-host mechanisms that drive disease and affect treatment response still need to be better defined.
Mtb infection begins after Mtb is inhaled into the lungs, where it infects local innate cells and leads to pulmonary tuberculosis. However, Mtb can disseminate via the bloodstream and airways to other organs, producing extrapulmonary disease. Understanding and characterizing the immune responses in these variant Mtb forms of disease is crucial for fine tuning therapies.
Tuberculous meningitis (TBM) is the most lethal form of TB, arising when Mtb infects the central nervous system (CNS) by reaching the cerebrospinal fluid (CSF) and meningeal spaces of the brain. Globally, TBM kills roughly half of affected adults, with mortality reaching as high as 70% in people with HIVco-infection. The stark difference in survival rates between TBM HIV+ and HIV- populations highlights the need to understand how and why HIVco-infection alters CNS immunity and treatment response.
Previous work from a TBM Uganda study from the Bold lab showed that higher CSF bacterial burden was associated with higher levels of inflammatory CSF cytokines and showed worse clinical outcomes than those with lower CSF Mtb burdens; thus, Bold and colleagues wanted to further parse out the role of inflammation in clinical outcomes.
In a TBM Vietnam study, Bold and colleagues found that patients with baseline hyper-inflammation had worse disease outcomes. This nicely recapitulated the previous findings in the Uganda study, in which higher levels of inflammation were associated with worse disease. Interestingly, after adjunctive corticosteroid treatment, the hyper-inflammation group saw better survival outcomes, whereas non-survivors had lower baseline concentrations of inflammatory CSF cytokine levels.
When the researchers looked at the TBM HIV+ subgroup, baseline CSF inflammatory cytokine concentrations were overall lower compared to the TBM HIV- group, but did not differ between survivors and non-survivors. Like the non-survivors in the TBM HIV- group, TBM HIV+ patients did not benefit from steroid therapy. Together, these findings led Gold and colleagues to hypothesize that hypo-inflammation may be contributing to poor clinical outcomes in TBM, especially within the context of HIV co-infection.
In order to generalize the previous results from the Vietnam study to other populations where HIV and TBM are prevalent, Bold and colleagues went back to examine baseline T-cell counts and CSF concentrations of cytokines, chemokines, and growth factors in Ugandan patients with HIV-associated TBM.
Results from the Uganda study underscored that non-survivors had markedly lower peripheral blood CD4 T-cell counts compared to survivors. Next, they looked at a broad panel of immune mediators in baseline CSF. This data revealed that CSF interferon-gamma (IFN-γ) was the cytokine most differentially expressed between groups, with survivors showing substantially decreased mortality across increasing IFN-γ concentration tertiles. The opposite was true for those with low IFN-γ concentrations, which had significantly higher mortality rates. Combined, the data revealed that impaired CD4 TH1 immunity may be behind the high mortality observed in TBM HIV+ populations.
To further test that point, peripheral CD4 T-cell counts were analyzed together with baseline CSF IFN-γ concentration levels. The TBM HIV+ subgroup with both profound CD4 depletion and low CSF IFN-γ baseline levels had the highest mortality, whereas the HIV+ subgroup with preserved CD4 counts and higher IFN-γ had increased survival rates. Taken together, these data support a model in which mortality in HIV-associated TBM is driven by hypo-inflammation due to inadequate local TH1 immunity.
Overall, Cytokines 2025 was an energizing first international conference that reignited my excitement for science. Stepping outside my usual niche of pulmonary tuberculosis and hearing such a wide range of talks gave me a much more well-rounded view of the current field.
Christina Gao: Symposium 11 – Cytokines in Inflammation I
In Symposium 11: Cytokines in Inflammation I, Dr. Katherine Barnett presented “Cell death, damage, and inflammation in viral infection”, a summary of her research on cell death responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human airway epithelium. While SARS-CoV-2 preferentially infects angiotensin-converting enzyme 2 (ACE2)-expressing epithelial cells, most studies on cell death and inflammation during the viral infection are attributed to ACE-negative myeloid cells. Barnett’s work fills the gap by elucidating how SARS-CoV-2 replication triggers cell death in host cells and how these responses coordinate inflammatory responses in bystander cells.
Barnett then asked how necroptosis is initiated in infected cells. Her findings suggested that viral replication directly drives necroptosis through Z-DNA–binding protein 1 (ZBP1), which binds Z-conformation nucleic acids formed during infection. To examine how this process correlates to inflammation in bystander cells, Barnett used Vero cells, which cannot produce type I interferon and are therefore highly permissive to viral infection, and peripheral blood mononuclear cells (PBMCs). When individually cultured, these cells produced little inflammatory response to SARS-CoV-2. When co-cultured, however, there was robust interleukin 1β (IL-1β) production. Barnett attributed this to damage-associated molecular patterns (DAMPs) and SARS-CoV-2 virions from infected cells that activate inflammasomes in myeloid cell populations.
This work is important because inflammation during SARS-CoV-2 infection drives disease severity. Insights into the mechanisms of cell death responses contribute to a more complete understanding of host defense. At the same time, this work raises questions for future investigation; for example, whether ZBP1 could be a viable therapeutic target for SARS-CoV-2 and prevent excessive inflammation without compromising immune responses.
Following Barnett’s presentation, Dr. Robyn Klein shared “Cytokines and virus-mediated memory impairment”, a snapshot of her work on postacute cognitive deficits, a condition affecting millions of people after SARS-CoV-2 infection. Despite its prevalence, the mechanisms underlying these deficits remain unclear. Klein’s work investigates how viral infection contributes to cognitive dysfunction and whether vaccines may provide protection.
Using mice infected with the Beta variant of SARS-CoV-2, Klein performed the open field test (OFT) and the novel object recognition (NOR) test to evaluate behavior after recovery. In the OFT, which involves placing mice in an empty enclosed box and assessing motor function and anxiety, both mock-injected control mice and SARS-CoV-2-recovered C57BL/6J mice behaved similarly. However, in the NOR test, which allowed the mice to explore two identical objects on training day, then replaced one with a novel object on test day, the control mice showed a preference for the novel object, whereas the recovered mice showed no discrimination between objects. These findings suggest that infection with the Beta variant of SARS-CoV-2 leads to memory impairment in C57BL/6J mice at postacute time points.
Upon investigating the mechanisms behind behavioral differences, Klein reported that IL-1 receptor 1 (IL-1R1) signaling in neural stem cells (NSCs) mediates acute loss of neurogenesis and memory impairment. Prior work has shown that overproduction of IL-1β in the hippocampus reduces neurogenesis. Here, mice lacking IL-1R1 in NSCs were protected from the acute loss of proliferating neuroblasts after infection. In the NOR test, the recovered control mice showed no discrimination, whereas the recovered-IL-1R1 knockout mice showed a preference for the novel object, indicating that the latter were partially protected from memory impairment. Importantly, vaccinated mice do not exhibit hippocampal IL-1β induction, loss of neurogenesis, or cognitive impairment after breakthrough infection.
Klein’s work offers a framework for understanding postacute cognitive deficits and points toward potential therapeutic and preventative strategies. While Klein briefly mentioned there were no behavioral differences between sexes, I wondered whether age would play a role, given that older individuals have naturally decreased neurogenesis. I am also curious about the genetic and environmental factors that may contribute to variations in susceptibility and severity of post-acute cognitive deficits.
These presentations and others at Cytokines 2025 helped me better appreciate the interdisciplinary nature of immunology, how collaborating with others and incorporating diverse perspectives can advance our scientific understanding. It was also rewarding to share my own work through a poster, to learn which aspects of my research were most interesting to others and recenter my motivation for the project.
