Cancer treatment: optimization of CAR T-cell therapy

LMU physician Sebastian Kobold
Photo Credit: © LMU / Stephan Höck

Scientific Frontline: Extended "At a Glance" Summary

The Core Concept: An advanced form of immunotherapy in which Chimeric Antigen Receptor (CAR) T cells are genetically engineered to resist immunosuppressive signals found within solid tumors, enabling the immune system to effectively destroy cancer cells that were previously resistant to treatment.

Key Distinction/Mechanism: While standard CAR T-cell therapy is highly effective against blood cancers, it often fails against solid tumors because a metabolite called prostaglandin E2 (PGE2) suppresses the T cells' function. This new approach involves removing the specific receptors on the T cells that PGE2 binds to; by eliminating these binding sites, the T cells become "deaf" to the tumor's suppression signal and remain active to attack the malignancy.

Origin/History:

• 2024: Professor Sebastian Kobold’s research group at LMU University Hospital identifies that PGE2 blocks T cells in the tumor vicinity.
• 2026: The team, in cooperation with the University of Tübingen, publishes their success in engineering PGE2-resistant cells in Nature Biomedical Engineering.

Major Frameworks/Components:

• Chimeric Antigen Receptor (CAR) T Cells: Patient-derived immune cells modified to recognize specific cancer proteins (like CD19).
• Prostaglandin E2 (PGE2): An immunosuppressive metabolite in the tumor microenvironment that normally inhibits immune response.
• Receptor Knockout: The genetic removal of PGE2 receptors from T cells to prevent immunosuppression.

Tiny marine animal reveals bacterial origin of animal defence mechanisms

Glass plates to catch the model organism Trichoplax in its natural habitat, warm coastal waters. Scientists at Kiel University use the tiny placozoan for evolutionary research.
Photo Credit: © Harald Gruber-Vodicka, Kiel University

Scientific Frontline: "At a Glance" Summary

• Main Discovery: The simple marine animal Trichoplax utilizes an ancient, bacteria-derived lysozyme for acidic extracellular digestion, proving that essential animal immune mechanisms evolved from early digestive processes.
• Methodology: Scientists characterized the enzyme in Trichoplax sp. H2 using proteomics and Western blotting, monitored in situ pH levels with fluorescence reporters, and reconstructed the enzyme's evolutionary history via structure-based phylogenetics.
• Key Data: The research identified a glycoside hydrolase family 23 (GH23) lysozyme that exhibits peak activity at pH 5.0, precisely matching the acidic environment generated within the animal's temporary feeding grooves during nutrient uptake.
• Significance: This study provides the first evidence that metazoan GH23 lysozymes originated from a horizontal gene transfer event from bacteria to a pre-bilaterian ancestor, functioning simultaneously in nutrition and pathogen defense.
• Future Application: Elucidating these ancient dual-use mechanisms clarifies the evolutionary trajectory of the innate immune system and may inform the development of bio-inspired antimicrobial agents.
• Branch of Science: Evolutionary Biology, Immunology, and Marine Biology
• Additional Detail: The lysozyme features a unique N-terminal cysteine-rich domain that stabilizes the protein during transport but is cleaved off to maximize enzymatic potency at the site of action.

Established cancer drug reactivates immunotherapy

Professor Florian Bassermann and his team are researching the role of the ubiquitin system in cancer. Insights from their basic research are quickly benefiting patients as well.
Photo Credit: Kathrin Czoppelt / TUM Klinikum

Scientific Frontline: Extended "At a Glance" Summary

The Core Concept: Researchers have identified that an existing cancer drug, carfilzomib, can restore the efficacy of CAR-T cell therapy in multiple myeloma patients by preventing cancer cells from hiding their surface markers.

Key Distinction/Mechanism: A common resistance mechanism in immunotherapy involves cancer cells degrading specific surface antigens (like BCMA) via the ubiquitin-proteasome system, effectively becoming invisible to engineered T cells. Unlike therapies that require new drug discovery, this method utilizes carfilzomib—a known proteasome inhibitor—to block this degradation process, restabilizing the antigens on the cell surface and allowing the CAR-T cells to recognize and attack the cancer again.

Origin/History: The findings were published in the journal Blood in 2026 by a team led by Prof. Florian Bassermann and Dr. Leonie Rieger at the Technical University of Munich (TUM).

Major Frameworks/Components:

• CAR-T Cell Therapy: A treatment where a patient's T cells are genetically modified to target cancer cells.
• BCMA (B Cell Maturation Antigen): The specific protein target on multiple myeloma cells.
• Ubiquitin-Proteasome System: The intracellular network responsible for degrading proteins, identified here as the cause of BCMA loss.
• Carfilzomib: An approved drug that inhibits the proteasome, preventing antigen degradation.

Shining New Light on How Cytokines Manage Immune Response

Green fluorescent tags delivered by the new CyCLoPs tool reveal cells that responded to a specific cytokine (IL-17A) in a mouse model.
Image Credit: Huh Lab

Scientific Frontline: "At a Glance" Summary

• Main Discovery: A new toolkit named CyCLoPs (cytokine cellular locating platforms) enables the precise tagging and visualization of cells that receive cytokine signals, illuminating previously invisible immune communication pathways.
• Methodology: Researchers engineered a system that functions as a biological highlighter; when a cytokine binds to a cell receptor, a fluorescent marker is released and travels to the cell nucleus, creating a durable tag that persists through cell division and allows for long-term tracking.
• Key Data: Validation in preclinical mouse models successfully identified cells responding to interleukin-17A in the small intestine and interferon gamma in tumors, with the latter experiment revealing that the cytokine unexpectedly weakened killer T cells.
• Significance: This technology addresses a critical gap in immunology by identifying exactly which cells receive immune signals and how they react, moving beyond the historical capability limited to observing only the cells that send these signals.
• Future Application: The platform supports the development of targeted therapies for infectious diseases, cancer, and autoimmune conditions by allowing scientists to observe immune responses over extended periods and in specific tissues.
• Branch of Science: Immunology and Molecular Biology
• Additional Detail: Current limitations exist regarding non-dividing cells such as neurons due to nuclear architecture or cell size, prompting the immediate development of a second-generation version to expand compatibility.

Building Immunity Against Avian Flu Risks

Plate test used to quantify infectious viral particles or neutralizing antibodies. Each hole corresponds to one viral particle.
Photo Credit: CDC

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers identified that specific cross-reactive antibodies acquired from seasonal influenza exposure or vaccination target the conserved "stem" region of the avian influenza A (H5N1) virus, providing a baseline level of protection against the disease.
• Methodology: The team analyzed immune responses across different population cohorts by comparing antibody levels in individuals vaccinated with an adjuvanted H1N1 vaccine during the 2009 pandemic against those receiving standard seasonal shots, while also examining the influence of birth year on immune imprinting.
• Key Data: Individuals who received the AS03-adjuvanted H1N1 vaccine exhibited a nearly fourfold increase in cross-reactive antibodies compared to a 30% increase from standard seasonal vaccines, and those born before 1965 showed naturally higher antibody levels due to childhood exposure to H1 or H2 subtypes.
• Significance: The study reveals that these antibodies do not prevent the virus from entering cells but instead inhibit its ability to detach and spread to neighboring cells, essentially trapping the virus and potentially reducing disease severity.
• Future Application: Findings support the strategic deployment of adjuvanted influenza vaccines to broaden population immunity, which could lower the antigen dose required for specific H5N1 vaccines and increase global vaccination capacity during a pandemic.
• Branch of Science: Immunology and Virology
• Additional Detail: The research underscores the concept of "immune imprinting," where the specific influenza subtype a person is exposed to in early childhood permanently shapes their immune system's ability to recognize and combat related viral strains later in life.

Blueprints for Designing T Cells that Kill

This image shows killer T cells surrounding and attacking a cancer cell. A new atlas developed by researchers at UC San Diego could make it possible to design custom T cells for immunotherapy to maximize patient benefit while minimizing potential negative effects.
Image Credit: National Institutes of Health/NIAID

Scientific Frontline: "At a Glance" Summary

• Main Discovery: A comprehensive genetic atlas of CD8+ T cell states was developed, identifying specific transcription factors that determine whether these immune cells persist as effective defenders or succumb to dysfunctional exhaustion.
• Methodology: Researchers utilized advanced computational modeling, gene editing, and in vivo mouse studies to map nine distinct T cell states and experimentally manipulated genetic switches to decouple the pathways regulating immune memory from those driving exhaustion.
• Key Data: The study identified nine distinct CD8+ T cell states and discovered two previously unknown transcription factors, ZSCAN20 and JDP2, which, when inhibited, restored tumor-killing capacity without sacrificing long-term immune memory.
• Significance: This research fundamentally challenges the long-standing scientific belief that T cell exhaustion is an inevitable byproduct of chronic immune activation, proving instead that exhaustion and protective memory are distinct, separable genetic programs.
• Future Application: These findings provide a blueprint for engineering "custom" T cells in adoptive cell transfer and CAR T-cell therapies that are programmed to resist burnout while maintaining long-term potency against cancer and chronic infections.
• Branch of Science: Immunology, Oncology, and Computational Biology.

Immunotherapy reduces plaque in arteries of mice

An immunotherapy reduces plaque in the arteries of mice, offering a potential new strategy to treat cardiovascular disease, according to a study led by WashU Medicine researchers. An artery from an untreated mouse (top) shows more plaque (orange) than that of a mouse treated with the antibody-based immunotherapy (bottom).
Image Credit: Junedh Amrute/WashU Medicine

Scientific Frontline: "At a Glance" Summary

• Main Discovery: An antibody-based immunotherapy successfully reduced atherosclerotic plaque volume and inflammation in murine models, demonstrating a novel ability to clear existing arterial obstructions rather than simply preventing new growth.
• Methodology: Researchers utilized single-cell profiling on human coronary arteries to identify "modulated smooth muscle cells" expressing fibroblast activation protein (FAP). They then engineered a bispecific T cell engager (BiTE) molecule to specifically target these FAP-expressing cells, directing the host immune system to destroy them.
• Key Data: The study analyzed over 150,000 cells from 27 human coronary arteries to isolate the specific molecular targets. In mouse models, the administration of the BiTE therapy significantly decreased total plaque burden and improved plaque stability compared to untreated controls.
• Significance: Unlike standard statin therapies that primarily prevent disease progression by lowering cholesterol, this approach actively eliminates established plaque and associated inflammatory cells, potentially offering a solution for patients who remain at high risk of heart attack despite controlled lipid levels.
• Future Application: This technology supports the development of precision medicine for advanced coronary artery disease and enables the use of PET/CT imaging tracers to distinguish between stable and unstable, rupture-prone plaques in clinical settings.
• Branch of Science: Cardiology and Immunology
• Additional Detail: The targeted modulated smooth muscle cells are functionally distinct from healthy structural cells, as they migrate to artery walls and secrete signals that recruit inflammatory immune cells, directly driving lesion instability.

A broken DNA repair tool accelerates aging

Fatal error: The failure of the repair enzyme SPRTN in these cultured cells leads to fatal errors in cell division, e.g. by distributing the chromosomes (red) to three daughter cell nuclei instead of two (arrow). Green: Cell division apparatus/cytoskeleton.
Image Credit: Institute of Biochemistry II, Goethe University Frankfurt

Scientific Frontline: "At a Glance" Summary

• Main Discovery: The failure of the DNA repair enzyme SPRTN not only causes genetic damage accumulation but also leads to nuclear DNA leaking into the cytoplasm, which triggers a chronic, aging-accelerating inflammatory response.
• Methodology: Researchers led by Prof. Ivan Ðikić utilized cell culture experiments and genetically modified mice to observe the physiological effects of SPRTN deficiency, specifically monitoring DNA distribution and immune signaling pathways.
• Key Data: In SPRTN-deficient models, chromosomes were observed distributing to three daughter cells instead of two; the resulting chronic inflammation was particularly pronounced in mouse embryos and persisted into adulthood, notably in the lungs and liver.
• Significance: This study establishes a critical link between DNA-protein crosslinks (DPCs), the cGAS-STING immune signaling pathway, and systemic aging, explaining the pathology of the rare hereditary disorder Ruijs-Aalfs syndrome.
• Future Application: Findings suggest that blocking specific immune responses triggered by cytoplasmic DNA could serve as a therapeutic strategy for Ruijs-Aalfs syndrome and other conditions driven by inflammation-associated aging.
• Branch of Science: Molecular Biology and Immunology
• Additional Detail: The cytoplasmic DNA is misidentified by the cell as a pathogen (like a virus), activating defense mechanisms that drive the systemic inflammation responsible for the premature aging phenotype.

Immunotherapy before surgery helps shrink tumors in patients with desmoplastic melanoma

Dr. Antoni Ribas (far right) with members of his research team at UCLA, who helped lead the clinical trial showing that immunotherapy before surgery can shrink or eliminate tumors in patients with desmoplastic melanoma.
Photo Credit: Courtesy of UCLA/Health

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Neoadjuvant treatment with the immunotherapy drug pembrolizumab significantly shrinks or eliminates tumors in patients with desmoplastic melanoma, a rare and aggressive form of skin cancer.
• Methodology: In the SWOG S1512 clinical trial (Cohort A), researchers administered three infusions of pembrolizumab over a nine-week period to 28 patients with surgically resectable desmoplastic melanoma prior to their scheduled surgery.
• Key Data: Pathologic analysis revealed that 71% of patients had no detectable live tumor cells at the time of surgery, and at the three-year follow-up, 95% of patients survived with a 74% disease-free recurrence rate.
• Significance: This therapeutic approach can spare patients from extensive, potentially disfiguring surgeries and postoperative radiation, drastically improving quality of life without compromising survival outcomes.
• Future Application: The findings support a paradigm shift toward using PD-1 blockade immunotherapy as the standard neoadjuvant care for resectable desmoplastic melanoma, replacing immediate invasive excision.
• Branch of Science: Oncology, Immunology, and Dermatology.
• Additional Detail: Desmoplastic melanoma, typically resistant to chemotherapy and radiation, was found to be highly responsive to PD-1 blockade due to its high mutational burden caused by UV damage.

Foundations for type 1 diabetes may already be laid during pregnancy

Image Credit: Scientific Frontline

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Patterns of inflammation and altered protein levels predictive of Type 1 Diabetes (T1D) are detectable at birth, indicating that the disease process may initiate during fetal development rather than commencing solely with the appearance of autoantibodies later in childhood.
• Methodology: Researchers analyzed cord blood samples from the All Babies in Southeast Sweden (ABIS) cohort, utilizing Olink proteomic analysis to compare 146 children who subsequently developed T1D against 286 matched controls.
• Key Data: A machine learning model based on a specific subset of proteins predicted T1D development with high accuracy (AUC = 0.89 ± 0.02), identifying risk years before the mean diagnosis age of 12.6 years.
• Significance: This finding shifts the understanding of T1D etiology by pinpointing a "pre-autoimmune" phase involving innate immunity and tissue remodeling pathways that are perturbed prenatally, independent of standard genetic risk factors.
• Future Application: The identification of these biomarkers offers a potential non-invasive screening method to detect high-risk infants immediately at birth, creating a new therapeutic window for primary prevention before beta-cell destruction begins.
• Branch of Science: Immunology and Proteomics.
• Additional Detail: The study linked these early protein alterations to specific environmental exposures, including perfluorinated substances (PFOS) and metabolic markers like stearic acid, suggesting environmental factors during pregnancy drive these early immune perturbations.

More Than Just Gut Cohabitants: How Gut Bacteria Control Immune Responses

The gut-brain axis is a bidirectional communication network linking the central nervous system with the enteric nervous system (the "second brain" in the gut) via neural, hormonal, and immune pathways.
Image Credit: Scientific Frontline / stock image

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Commensal gut bacteria utilize type III secretion systems, previously thought exclusive to pathogens, to inject effector proteins directly into human cells and actively manipulate host immune responses.
• Methodology: The research consortium constructed a large-scale interactome map identifying over 1,000 protein-protein interactions between bacterial effectors and human host proteins, validated by functional assays of immune signaling pathways.
• Key Data: Analysis revealed that genes encoding these secretion systems are significantly enriched in the microbiomes of patients with Crohn’s disease, with specific proteins targeting the NF-κB signaling pathway and cytokine responses.
• Significance: These findings fundamentally shift the understanding of the microbiome from correlation to causation, demonstrating that non-pathogenic bacteria are active agents capable of directly modulating human physiology and inflammation.
• Future Application: This mechanistic insight facilitates the development of targeted therapeutic strategies that modulate specific bacterial-host interactions to treat inflammatory bowel diseases and potentially other autoimmune disorders.
• Branch of Science: Microbiology, Immunology, and Network Biology
• Additional Detail: The study specifically highlights the modulation of Tumor Necrosis Factor (TNF) activity, a key cytokine in inflammation, providing a molecular basis for the efficacy of anti-TNF therapies in Crohn's disease.

Why do T cells attacking tumors become fatigued?

Illustration Credit: Courtesy of Kyoto University

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Accumulation of active aldehydes, driven by lipid peroxidation, induces CD8⁺ T cell (killer T cell) exhaustion in the tumor microenvironment by disrupting the balance of cellular energy metabolism.
• Methodology: Researchers employed multicolor flow cytometry to analyze mitochondrial function and metabolic activities in tumor-infiltrating T cells derived from human samples and mouse models with genetic deficiencies in fatty acid oxidation (FAO) enzymes.
• Key Data: Deficiency in FAO enzymes resulted in excessive fatty acid uptake and subsequent lipid peroxidation; the resulting active aldehydes inhibited FAO while simultaneously activating glycolysis, creating a self-perpetuating cycle of metabolic failure.
• Significance: Elucidates a critical, previously undefined mechanism where active aldehydes force T cells into terminal exhaustion by rewiring metabolism, distinct from the cell death pathway of ferroptosis.
• Future Application: Development of therapeutic strategies that target and neutralize active aldehydes to disrupt this metabolic exhaustion cycle, thereby sustaining T cell functionality during cancer immunotherapy.
• Branch of Science: Immunology, Oncology, and Metabolomics
• Additional Detail: The findings overturn the prior assumption that lipid peroxidation affects T cells primarily through ferroptotic cell death, highlighting instead a non-lethal but debilitating metabolic reprogramming.

Scientists develop molecules that may treat Crohn’s disease

Broad scientists designed molecules (pictured in teal) that can bind CARD9 (white with red and blue), a protein linked to inflammatory bowel disease.
Image Credit: Rush et al. Cell. DOI: 10.1016/j.cell.2025.12.013

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers developed small-molecule drug candidates that mimic a rare, protective variant of the CARD9 gene to treat Crohn's disease and other inflammatory bowel diseases.
• Methodology: The team utilized a "binder-first" strategy, screening 20 billion molecules to identify binders to the CARD9 coiled-coil domain, followed by X-ray crystallography and competitive binding assays to isolate compounds that block inflammatory signaling.
• Key Data: The initial library screen evaluated over 20 billion compounds, ultimately yielding molecules that significantly reduced inflammation in both human immune cells and a mouse model expressing the human CARD9 gene.
• Significance: This work validates a complete "genetics-to-therapeutics" pipeline, proving that scaffolding proteins previously considered "undruggable" can be effectively targeted by mimicking naturally occurring protective variants.
• Future Application: Immediate efforts focus on optimizing these compounds for human clinical trials, while the broader methodology provides a blueprint for developing drugs against other difficult genetic targets.
• Branch of Science: Chemical Biology, Immunology, Genetics, and Molecular Biology.
• Additional Detail: The development strategy parallels the success of PCSK9 inhibitors for cholesterol, leveraging the safety profile of a natural genetic variant to guide drug design.

“Recipe book” for reprogramming immune cells

Filipe Pereira, professor of molecular medicine at Lund University
Photo Credit: Courtesy of Lund University

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers at Lund University established a high-throughput screening platform and a library of over 400 immune-related transcription factors to decode the specific "recipes" required to reprogram accessible somatic cells into distinct immune cell identities.
• Methodology: The study utilized unique DNA barcodes attached to each transcription factor, allowing the simultaneous tracking of thousands of combinatorial possibilities to determine which specific factor groups drive conversion to desired immune lineages.
• Key Data: This four-year project successfully identified reprogramming protocols for six different immune cell types, including Natural Killer (NK) cells, which were previously impossible to generate through direct reprogramming.
• Context: Prior to this breakthrough, the specific reprogramming factors had been mapped for only four of the human body's more than 70 distinct immune cell types, limiting the development of synthetic immunotherapies.
• Significance: The platform enables the production of rare, patient-specific immune cells from abundant sources like skin fibroblasts, potentially expanding immunotherapy applications from cancer treatment to autoimmune diseases and regenerative medicine.

A bacterial toxin can counteract colorectal cancer growth

Sun Nyunt Wai
Photo Credit: Mattias Pettersson

Scientific Frontline: "At a Glance" Summary

• Discovery of Anti-Tumor Toxin: The purified cytotoxin MakA, secreted by the cholera bacterium Vibrio cholerae, has been identified as an agent that significantly inhibits the growth of colorectal cancer tumors.
• Mechanism of Action: MakA accumulates specifically within tumor tissue, inducing cancer cell death and suppressing proliferation while simultaneously recruiting innate immune cells, such as macrophages and neutrophils, to the tumor microenvironment.
• Safety and Specificity: In murine models, systemic administration of MakA targeted tumors locally without causing harmful systemic inflammation, weight loss, or organ dysfunction, indicating a high degree of specificity for cancerous tissue.
• Immune Modulation: The toxin alters the cellular composition of the tumor environment, stimulating the production of immune mediators that promote apoptosis while preserving regulatory mechanisms to protect surrounding healthy tissue.
• Therapeutic Potential: This study highlights a novel therapeutic avenue utilizing bacterial toxins to both directly target cancer cells and enhance the host's immune response, offering a potential alternative to traditional treatments like chemotherapy and radiation.

When a virus releases the immune brake: New evidence on the onset of multiple sclerosis

Fluorescence microscope image of a mouse brain. The protective myelin layer (red) surrounds the nerve cell extensions. Cells infected with a virus are visible in light blue. Such infections cause immune cells to invade the brain and attack the myelin layer.
Image Credit: Hyein Kim, University of Basel

Scientific Frontline: "At a Glance" Summary

• Discovery of Initiation Mechanism: Researchers have identified a specific biological sequence where the Epstein-Barr virus (EBV) triggers early multiple sclerosis (MS)-like damage by allowing self-reactive B cells to bypass immune checkpoints.
• Molecular Mimicry: The mechanism relies on a viral protein (Latent Membrane Protein 1) that mimics a crucial "approval" signal usually provided by other immune cells, preventing the programmed elimination of B cells that target the body's own proteins.
• Localized Pathogenesis: Experimental mouse models demonstrated that these "out-of-control" B cells capture myelin antigens and cause localized demyelinating lesions in the central nervous system, mirroring the earliest stages of MS.
• B Cell Direct Action: The study shifts the understanding of B cells from indirect influencers of inflammation to direct agents of lesion formation, suggesting they are the primary "spark" for chronic brain inflammation.
• Therapeutic Correlation: The findings explain the clinical efficacy of current B-cell depleting therapies and emphasize that MS risk is shaped by the timing and sequence of rare immune events rather than infection alone.
• Future Prevention: This discovery highlights the potential for preventive strategies, such as targeted vaccinations designed to inhibit severe EBV infections and prevent the subsequent invasion of the brain by pathogenic B cells.

TB harnesses part of immune defence system to cause infection

Photo Credit: Thirdman

Scientific Frontline: "At a Glance" Summary

• Mycobacterium tuberculosis (MTB) Subverts Immune Defense: The bacterium exploits Dectin-1, an immune receptor typically tasked with anti-fungal defense, to facilitate its own survival and replication within host cells rather than being destroyed.
• Mechanism of Action: Research reveals that MTB produces a unique alpha-glucan molecule that specifically targets the Dectin-1 receptor, manipulating host cell responses to create a favorable environment for infection.
• Experimental Evidence: In controlled studies involving human and mouse cells, the absence of the Dectin-1 pathway allowed for better control of the infection; specifically, mice lacking this receptor were found to be significantly more resistant to MTB.
• Global Context: This discovery addresses a critical knowledge gap regarding why humans and animals are highly susceptible to TB, a disease responsible for approximately 1.5 million deaths annually.
• Future Implications: Identifying this pathway offers potential for new therapeutic interventions and preventive strategies, such as genetically modifying livestock to remove the Dectin-1 receptor and increase herd resistance.

Stanford Medicine study identifies immune switch critical to autoimmunity, cancer

Edgar Engleman, MD, professor of pathology
Photo Credit: Courtesy of Stanford School of Medicine

A single signaling pathway controls whether immune cells attack or befriend cells they encounter while patrolling our bodies, researchers at Stanford Medicine have found. Manipulating this pathway could allow researchers to toggle the immune response to treat many types of diseases, including cancers, autoimmune disorders and those that require organ transplants.

The research, which was conducted in mice, illuminates the mechanism of an important immune function that prevents inappropriate attacks on healthy tissue. Called peripheral immune tolerance, the key cellular players, known as regulatory T cells (or Tregs, pronounced “tee-regs”), were first described in the late 1990s in a series of discoveries that were recently recognized with the 2025 Nobel Prize in physiology or medicine.

A platform to test new cancer treatments

Differentiated hepatic cells growing in a flask re-gain the appearance of cells present in liver.
Image Credit: © FAMOL, UNIGE

Overcoming acquired treatment resistance is one of the major challenges in the fight against cancer. While combination therapies hold promise, their toxicity to healthy tissue remains a major hurdle. To anticipate these risks, researchers at the University of Geneva (UNIGE) have developed in vitro models of the kidneys, liver, and heart – three organs particularly sensitive to such therapies. This fast, animal-free approach paves the way for safer evaluation of new treatments. The findings are published in Biomedicine & Pharmacotherapy. 

Recent advances in immunotherapy, targeted therapies, and gene therapies have significantly improved survival rates for patients with cancer. However, over time, many tumors develop resistance to these treatments, undermining their effectiveness. This phenomenon, known as ‘acquired resistance’, has become one of the major challenges in oncology. 

Immune system keeps mucosal fungi in check

The yeast fungus Candida albicans (blue) breaks out of human immune cells (red) by forming long thread-like cells called hyphae. The part of the hypha that has already left the immune cells is colored yellow.
Image Credit: Erik Böhm, Leibniz-HKI

The yeast Candida albicans colonizes mucosal surfaces and is usually harmless. However, under certain conditions it can cause dangerous infections. A research team at the University of Zurich has now discovered how the immune system prevents the transformation from a harmless colonizer to a pathogenic mode. This happens, among other things, by sequestering zinc. 

The microbiome not only consists of bacteria, but also of fungi. Most of them support human and animal health. However, some fungi also have pathogenic potential. For instance, the yeast Candida albicans can grow in an uncontrolled manner on the oral mucosa, causing oral thrush. 

In severe cases by growing in a filamentous form, it can enter the bloodstream and cause systemic infections, which account for over one million deaths per year. This happens primarily in people with a weakened immune system on intensive care units, for instance individuals who are immunosuppressed because of a transplantation or cancer.