Blood-stage malaria transiently depletes and remodels splenic macrophages, but how distinct subsets recover remains unclear. A recent report by Mauel et al. shows that a yolk sac-derived CD163high red pulp macrophage subset is selectively and durably lost after malaria, disrupting a growth differentiation factor 15-dependent circuit that supports marginal metallophilic macrophages.

Immune checkpoint blockade is usually framed as a T cell-directed therapy. Recent studies challenge this view by showing that B cells, plasma cells, and tumor-reactive antibodies are reshaped by programmed cell death protein-1 and cytotoxic T-lymphocyte-associated protein-4 blockade and can contribute to efficacy. Humoral immunity should therefore be integrated into models of checkpoint efficacy.

CD8+ T cells eliminate infected and malignant cells through coordinated proliferation and effector differentiation, processes supported by metabolic reprogramming that together form an interconnected, cross-regulated network. Emerging evidence indicates, however, that cell cycle progression and effector programming can be transiently uncoupled, with implications for T cell function and fate. Short-term modulation of cell cycle dynamics creates a window for metabolic rewiring, reshaping nutrient utilization, cytokine responsiveness, and bioenergetic capacity. This uncoupling can enhance T cell expansion, effector function, and antitumor activity. Collectively, these findings indicate that the cell cycle functions as an instructive checkpoint integrating metabolic and differentiation programs, not merely supporting proliferation. Understanding this interplay provides a conceptual framework to optimize T cell-based immunotherapies and rationally design chemoimmunotherapy combinations.

Follicular regulatory T (Tfr) cells enter the B-cell follicle and germinal center, where they control the magnitude, specificity, and duration of the antibody response. However, the temporal and spatial determinants of Tfr differentiation are incompletely understood. Recent advances in fate-mapping, single-cell transcriptomics, and human tissue analyses have revealed that Tfr cells differentiate progressively through distinct differentiation states, a process directed by follicular helper T cells. Tfr differentiation states have unique transcriptional identities, functional roles, and stabilities revealing intricate feedback loops controlling humoral immunity. Here, we review recent findings on the origins and functions of Tfr cells in mice and humans, how these subsets are intrinsically and extrinsically controlled, and how targeting these pathways may treat human disease.

Inborn errors of immunity (IEIs) are a group of disorders caused by defects in the immune system. Emerging evidence indicates that dysregulated interferon (IFN) signaling can perturb hematopoietic stem cells in nonhematological IEIs. This forum examines the role of IFNs in regulating hematopoiesis to inform prognosis and therapeutic strategies in IEI.

The immune system balances protective immunity against pathogens with tolerance to self and selected foreign antigens. Emerging evidence identifies erythropoietin (EPO) as a systemic immunoregulatory signal that links physiological stress to immune adaptation. Beyond its canonical role in erythropoiesis, EPO–EPO receptor (EPOR) signaling reprograms specialized myeloid cells, including macrophages and type 1 conventional dendritic cells (cDC1s), promoting efferocytosis, inflammatory restraint, and maturation-associated cDC1 fate. Through these mechanisms, EPO shapes antigen-specific T-cell responses across transplantation and cancer. We propose that the EPO–EPOR axis functions as a systemic regulator of immune adaptation through myeloid-cell programming.

Dendritic cells (DCs) are professional orchestrators of the immune system, integrating environmental signals to initiate, modulate, and sustain antitumor immunity. Although their therapeutic potential extends beyond antigen delivery, most clinical strategies have used DCs primarily as cellular vaccines. Here, we propose that DCs should be viewed as programmable therapeutic cells whose functions can be rationally controlled, either in situ or ex vivo, through four variables: DC identity, antigenic input, anatomical site of action, and immune-instructive output. Together, these variables determine how DCs establish tissue-level immune circuits for tumor control. We further discuss how tumor-associated barriers determine DC programming requirements and how matching DC programs to these microenvironmental or systemic barriers may improve tumor control in patients with cancer.

Natural killer (NK) cell immunotherapies remain less effective in solid tumors than in hematologic malignancies. Poor infiltration, checkpoint engagement, and metabolic stress contribute, but these mechanisms often operate within spatially organized niches. We develop the concept of spatially instructed checkpoints: inhibitory programs locally induced or maintained whose functional impact depends on position. We organize evidence across tissue-level exclusion, suppressive cellular neighborhoods, and the cytotoxic synapse, distinguishing causal findings from associations and hypotheses. Spatial organization is an integrating layer that interacts with, rather than replaces, intrinsic, soluble, metabolic, transcriptional, and epigenetic mechanisms. We propose a translational framework for converting spatial discoveries into deployable assays that identify the dominant barrier and guide mechanism-matched strategies to restore antitumor NK cell activity.

Clinical immunology is increasingly recognizing diet not merely as baseline metabolic sustenance but as a tunable pharmacological tool. By targeting conserved nutrient-sensing networks and the microbiome, defined nutritional protocols—such as fasting mimetics and specific macronutrient titrations—can actively rewire immune responses. In this review, we examine how manipulating macronutrient stoichiometry, systemic energy availability, and chrononutrition can be strategically deployed to enhance antitumor immune efficacy, promote tissue regeneration, and drive the resolution of chronic inflammation. Finally, we dissect the translational bottlenecks that must be overcome to elevate dietary strategies from broad lifestyle guidelines to prescribable precision immunotherapies.

Certain human leukocyte antigen (HLA) alleles occur more often in people with immune-mediated inflammatory diseases (IMIDs) than in unaffected individuals, making HLA one of the strongest inherited contributors to IMID risk. Yet how these alleles promote disease remains unclear. We argue that HLA risk has often been studied through allele-level properties or immunopeptidomic profiles without knowing which antigenic exposures matter. These approaches characterize peptide binding and presentation but rarely identify disease-relevant exposures. We propose that large-scale T cell receptor repertoire analysis provides a complementary route by identifying disease-associated clonotypes as antigenic footprints. When interpreted in their HLA context, these antigenic footprints can focus immunopeptidomic and functional studies on candidate antigens, turning HLA associations from statistical signals into testable mechanisms of disease.

I earned my PhD from the University of Science and Technology of China (USTC) and was a postdoc at the USTC Institute of Immunology. Now I am a Professor and Doctoral Supervisor at the same institute. My research focuses on reproductive immunology, particularly decidual natural killer (dNK) cells. I defined a pro-fetal-growth dNK subset and, more broadly, I study the plasticity of immune cells at the maternal–fetal interface and their implications in pregnancy disorders and neurodevelopmental defects in offspring.

I am a professor at Karolinska Institutet and a senior consultant in clinical microbiology at Karolinska University Hospital in Stockholm, Sweden. My research focuses on human natural killer (NK) cell biology, tissue immunity, viral infections, and cancer. My daughter Aida was born in September 2025, when I had been an independent group leader for a little more than 10 years and was a professor. I am currently in a 6-month period as her primary caregiver.

My laboratory focuses on natural killer (NK) cell and type 1 innate lymphoid cell (ILC)1 biology, with a particular interest in the development, heterogeneity, and functions of liver NK cell and ILC1 subsets. This interest stemmed from my PhD work in Professor Zhigang Tian’s laboratory at the University of Science and Technology of China, where I identified a liver-resident NK cell subset (later termed ‘ILC1s’). I remained in the same laboratory as a group leader to pursue this line of research.

Multiple myeloma remains incurable despite therapeutic advances. Longitudinal profiling of bone marrow and peripheral blood by Chander et al. reveals selective persistence of malignant plasma cell states, compartment-specific immune remodeling, incomplete humoral recovery after autologous stem cell transplantation, and divergent vaccine responses.

Metastasis is an inefficient cellular process in which most disseminated tumor cells fail to form secondary lesions in distant tissues due to hostile conditions, such as protective immune surveillance. The few cells that survive these threats can seed subclinical metastatic lesions, known as micrometastases, which are the least-known stage of the metastatic cascade. In this study, we review micrometastasis immunobiology, which differs from that of larger, clinically manifested metastasis. Key mechanisms such as epithelial-to-mesenchymal transition, stemness, dormancy, and immune evasion shape this bottleneck of metastasis, determining long-term disease evolution, therapy responses, and patient outcomes. Understanding micrometastasis immunology may reveal therapeutic opportunities to fully eradicate disseminated cells. Thus, we discuss emerging time-tailored immunopreventive strategies to intercept the progression to overt metastasis.

Most individuals infected with Mycobacterium tuberculosis never develop active disease, yet the airway immune events determining outcome remain poorly understood. Branchett and colleagues prospectively profiled bronchoalveolar lavage from recent tuberculosis contacts, revealing that progression reflects a dynamic competition between opposing local immune states rather than a single immunological failure.

Cytokines are key messenger molecules that bridge the nervous and immune systems through a bidirectional signalling network. Beyond their roles in development and homeostasis, neuronal cytokine sensing allows the central nervous system (CNS) to detect early immune perturbations, such as those triggered by emerging infections. Because neurons are postmitotic cells, rapid antipathogen responses are essential to prevent cell loss and ensure host survival. However, when CNS inflammation persists, as in chronic neuroinflammatory conditions such as multiple sclerosis or in age-associated inflammageing, cytokine signalling can become maladaptive and drive disease pathology. This review examines recent findings and emerging tools for studying how CNS neurons sense and respond to cytokines in both health and disease.

The underlying mechanism of tumor microenvironment-induced dysfunction of conventional type 1 dendritic cells (cDC1) remains unclear. Zhang et al. identify transforming growth factor β-driven coactivator-associated arginine methyltransferase 1 (CARM1) as an epigenetic inhibitor of cDC1 cross-presentation. CARM1 is a cell-intrinsic brake, and its inhibition represents a multi-pronged tumor immunotherapy strategy.

Maternal milk antibodies are garnering increasing interest. While IgA dominates the milk antibody literature, IgG is emerging as a critical source of protection for the hyporesponsive neonate against life-threatening infections and as an important factor in instructing developing immunity. In this forum article, we reframe milk IgG from a minor constituent to a central protagonist in vertically transmitted postnatal immunity.

Exercise reshapes host physiology and immunity, yet the mechanisms linking physical activity to disease protection remain incompletely defined. Emerging evidence indicates that exercise remodels the gut microbiome, producing compositional and metabolic adaptations that can regulate immune function. In this Review, we discuss how exercise-responsive microbiota and microbial metabolites, including short-chain fatty acids, secondary bile acids, and the one-carbon metabolite formate, influence systemic inflammation, antitumor CD8 T-cell immunity, autoimmunity, and metabolic disease. Defining causal taxa, microbial metabolic pathways, and host-sensing mechanisms may enable microbiome-informed exercise prescriptions and targeted metabolite-, probiotic-, or postbiotic-based therapies.

Mitochondrial complex II, succinate dehydrogenase (SDH), links the tricarboxylic acid cycle to the electron transport chain by oxidizing succinate to fumarate and reducing ubiquinone. This unusual position gives Complex II control over bioenergetics, redox state, succinate signaling, and chromatin regulation. In immune cells, Complex II regulates macrophage responses via the succinate–hypoxia-inducible factor-1α–IL-1β axis, T-cell proliferation, lineage commitment, and cytotoxicity. In target tissues of an aberrant immune attack, such as the intestinal epithelium and stem-cell compartments, SDHA loss lowers tissue tolerance, promotes inflammatory memory through succinate-driven epigenetic reprogramming, and amplifies immune-mediated injury. In tumors, SDH loss increases antigen presentation and their susceptibility to T-cell killing. Complex II, therefore, regulates immunopathology through its actions within both attacking immune cells and injured target tissues.

I am an immunologist and group leader at the Institute of Health and Medicine, Hefei Comprehensive National Science Center in China, where I established my laboratory in 2022. My laboratory focuses on alveolar macrophages—specifically, their development and functions in both homeostasis and disease, as well as their optimization for therapeutic applications. My two postdoctoral experiences each brought a major milestone: my daughter Emma was born while I was at the University of Science and Technology of China, and my daughter Bella arrived during my time at ETH Zurich in Switzerland.

A recent report by Fan et al. identifies trans-vaccenic acid, a maternal diet-derived lipid transferred through breast milk, as a key regulator of neonatal T-cell development. Beyond identifying a single bioactive metabolite, this study positions breast milk as a source of developmental signals that shape lifelong immune competence.

Natural killer (NK) cells are effectors of innate antitumor immunity, yet their therapeutic potential in solid tumors remains largely unrealized. Breast cancer exemplifies this paradox: NK cells are present in circulation and detectable within tumors, but their cytotoxic activity is limited. Recent advances in single-cell and spatial profiling reveal that NK-cell failure in breast cancer does not result from simple immune absence but from multilayered constraints imposed by the tumor ecosystem. Soluble mediators, metabolic pressures, stromal architecture, and suppressive immune networks reprogram NK-cell identity and uncouple activation from cytotoxicity. Understanding how these constraints shape NK-cell states reframes breast cancer as a model of innate immune dysfunction and highlights new opportunities to reestablish NK-cell function through immunotherapies.

Immune surveillance of the central nervous system (CNS) is regulated by the brain barriers. Antigen presentation at the blood–brain barrier (BBB) has been proposed to promote antigen-specific T-cell entry into the CNS, largely based on in vitro studies. Recent in vivo and transcriptomic studies call for a reassessment of this concept. In healthy mouse and human CNS endothelium, major histocompatibility complex (MHC) class I expression is low, and MHC class II is minimal to absent. During neuroinflammation, brain microvascular endothelial cells (BMECs) can acquire antigen-presenting features, predominantly in the context of strong or prolonged inflammation. We propose that BMEC antigen presentation amplifies vascular pathology rather than initiating CNS T-cell entry during immune surveillance or disease.

Emerging evidence now points to innate tissue immunity as a critical orchestrator of both local tissue adaptation and long-range hematopoietic reprogramming, including the amplification of emergency granulopoiesis through bone marrow progenitor remodeling. These findings position the intestine as an instructive niche capable of imprinting long-lived changes both locally and systemically. This review synthesizes current findings at the intersection of gut and bone marrow biology, examining how intestinal inflammation shapes granulopoietic output and how bone marrow-derived effectors, in turn, reinforce maladaptive tissue responses that underlie chronic intestinal manifestations, including colitis-associated cancer and extraintestinal inflammatory complications frequently seen in IBD. We delineate the physiological framework governing these regulatory nodes and highlight the translational implications for next-generation therapeutic intervention.

Spatial multi-omics of aging human lymph nodes by Fan and colleagues reveals that immunosenescence manifests as focal B cell coalescence into ‘SenSpots’ within germinal centers, where concerted epigenetic, transcriptional, proteomic, and metabolic reprogramming spatially orchestrates the decline of humoral immunity.

My research focuses on the fundamental biology of MAIT cells, a population of metabolite-sensing unconventional T cells. I investigate their roles in host defence and allergy, I also define MR1-presented antigens and the way they are recognised, with the aim of harnessing or inhibiting their function therapeutically.

CD8+ T cell exhaustion is increasingly recognized as a regulated adaptation to chronic antigenic stimulation rather than a simple immune failure. Indeed, recent studies reveal that exhaustion is imprinted early after T cell activation, integrating transcriptional and epigenetic cues to balance effector function with long-term persistence. Key regulators, including Inhibitor of DNA binding 3 (ID3), Thymocyte selection high mobility box protein (TOX), MYB, Krüppel-like factor 2 (KLF2), and Special AT-rich sequencing binding protein 1 (SATB1), orchestrate this process, preserving stem-like precursor populations that sustain immunity during chronic infection and cancer. This emerging view frames exhaustion as a context-dependent extension of the memory program rather than its collapse. By defining the molecular and functional logic of exhaustion, we highlight how these insights can inform new approaches to manipulate T cell fate for therapeutic benefit.

Homing pigeons’ navigation in darkness relies on Earth’s magnetic field. However, the underlying mechanism of magnetoreception remains poorly understood. Recently, Lisowski et al. demonstrated that superparamagnetic hepatic macrophages are potential magnetoreceptors that detect and transmit geomagnetic information to support the navigation of pigeons.

I am a cancer biologist with a strong interest in B-cell biology, lymphoma evolution, and autoimmunity. I had my daughter in 2024 while completing my postdoctoral research in Professor Andrejs Braun’s laboratory at Barts Cancer Institute, Queen Mary University of London. Although I was entitled to up to 1 year of maternity leave, I chose to take 7 months. What initially felt like a pause in my career became a meaningful period of reflection on my scientific direction, priorities, and long-term goals.

Hepatocellular carcinoma (HCC) remains one of the most lethal malignancies, characterized by a highly complex and dynamic tumor microenvironment in which tumor-associated macrophages (TAMs) are particularly abundant. TAMs regulate tumor initiation, progression, metastasis, and therapy response, making them attractive targets. However, targeting TAMs remains challenging due to their remarkable plasticity and functional heterogeneity. Recent high-throughput multi-omics studies have revealed that the HCC microenvironment consists of distinct regions defined by cellular architecture, such as the fibrotic invasive margin, perivascular niche, poorly vascularized hypoxic/necrotic areas, and cancer stem cell niche, each associated with unique protumorigenic properties. This review summarizes TAM heterogeneity across liver niches, disease stages, and treatment contexts, and evaluates TAM-targeted strategies, emphasizing key unresolved challenges to improving HCC outcomes.

More than 4 decades after the discovery of MHC restriction, it is clear that the phagocytosis of dying cells is not the only route by which macrophages acquire antigens. Fan and colleagues further expand this paradigm by showing that macrophages can sample a living cell’s cytosol and bypass classical endolysosomal processing.

Macrophages are central regulators of immunity, tissue homeostasis, and repair, whose plasticity enables them to integrate cues from their local microenvironment. Dysregulated macrophages contribute to chronic inflammation, fibrosis, impaired wound healing, and tumor progression. Biomaterials enable the modulation of macrophages through localized delivery of immunomodulatory signals and by creating instructive microenvironments. In this review, we examine macrophage–biomaterial interactions, emphasizing how surface chemistry, topography, mechanics, porosity, and degradation profiles shape macrophage recruitment and phenotype. We discuss emerging strategies for macrophage modulation, including programmable systems that provide spatiotemporal control over immune signaling. We further highlight how these applications can improve disease outcomes. Finally, we discuss design considerations, characterization, and translational challenges that must be overcome to advance macrophage-targeted biomaterials toward clinical implementation.

CD8+ T cell dysfunction, characterized by impaired effector function, proliferative capacity, and sustained inhibitory receptor expression, limits immune control in both cancer and chronic viral infections. Despite arising from distinct disease processes, these conditions induce a shared state of CD8+ T cell dysfunction, suggesting convergence on common regulatory pathways. Adenosine (ADO), an immunosuppressive purine metabolite generated through extracellular ATP catabolism, has emerged as a context-integrating metabolic checkpoint that regulates immune responses in response to tissue stress and inflammation. Across tumors and HIV, dysregulated ADO signaling reinforces checkpoint pathways and stabilizes dysfunctional CD8+ T cell states. In this review, we examine how the ADO–adenosine deaminase-1 axis shapes CD8+ T cell dysfunction across disease contexts and discuss its potential as a broadly applicable target for immune restoration.

Interleukin-33 (IL-33) is classically viewed as an alarmin, but in cancer, it may do more than merely initiate immunity. I propose that IL-33 scripts the trajectory of immunity through interconnected regulatory layers that influence how host responses are organized and ultimately resolved into either productive antitumor immunity or suppressive, repair-like states.

Mitochondrial calcium (mtCa2+) has long been framed as a bioenergetic regulator, yet evidence redefines it as a relevant immunometabolic switch. Within the tumor microenvironment, the mitochondrial calcium uniporter (MCU) complex and the NCLX–TMEM65 efflux axis maintain a ‘Goldilocks zone’ of Ca2+ homeostasis. This can be exploited by cancer cells to sustain oxidative phosphorylation and tricarboxylic acid-derived oncometabolite production, including succinate, fumarate, and 2-hydroxyglutarate, while imposing ionic and nutrient constraints on infiltrating immune cells. Chronic mtCa2+ overload in effector T cells drives mitochondrial dysfunction and exhaustion, while oxidative phosphorylation-dependent Ca2+ flux enforces the acquisition of an immunosuppressive profile in macrophages. Disrupting these tumor–immune ionic imbalances through selective MCU modulation or efflux pathway targeting offers a strategy to restore immune surveillance and/or enhance immune checkpoint inhibitor therapies.

Antibody–drug conjugates (ADCs) selectively deliver potent chemotherapeutic agents to tumor cells. In clinical settings, the therapeutic benefits of ADCs can be improved when combined with immune checkpoint inhibitors, probably due to the immunogenic nature of ADC-induced tumor cell death, which releases tumor antigens to be cross-presented by conventional type-1 dendritic cells (cDC1). This opinion article proposes that cDC1-mediated cross-presentation and cross-priming represent a central, still poorly understood, and underexploited immunological mechanism that links ADC-induced tumor cell death to durable antitumor immunity. Such mechanisms open opportunities for combinations with established and experimental immunomodulatory agents. Aside from checkpoint inhibitors, synergy has also been observed with agonist monoclonal antibodies directed to costimulatory receptors, increasing the potency of the ensuing antitumor immune response.

Growing evidence indicates that gut microbiota-derived metabolites are key regulators of immunometabolism in inflammatory bowel disease (IBD). Intestinal epithelial cells and immune cells exhibit profound metabolic alterations in IBD. Microbial metabolites act as intermediates in host–microbe communication, reshaping mitochondrial functions and cellular metabolic pathways, thereby impacting immune functions. Dysbiosis may, therefore, perturb immune homeostasis by rewiring host metabolic circuits. Understanding how microbial metabolites orchestrate immunometabolic crosstalk in the gut and leveraging it to recalibrate host immunometabolic circuits represents promising, underexplored therapeutic avenues. In this review, we highlight emerging concepts on how gut microbiota-derived metabolites shape immune cell immunometabolism and discuss the therapeutic potential of targeting the microbiota–metabolite–immunometabolism axis in IBD.

Inflammation is a metabolically intensive and tightly regulated process, driven primarily by innate immune cells. Cellular metabolism actively instructs immune signaling and cell fate decisions. Bioenergetic pathways, including glycolysis, mitochondrial respiration, and the tricarboxylic acid cycle, reshape cytokine production and regulate inflammatory cell death pathways. In this review, we synthesize emerging evidence on how metabolic intermediates and pathways regulate inflammasome signaling and the execution of diverse inflammatory cell death modalities, including pyroptosis, necroptosis, PANoptosis, and ferroptosis. We propose that metabolic inputs—including redox balance, mitochondrial dynamics, and lipid modifications—constitute an interconnected metabolic regulatory network that determines the threshold and outcome of inflammatory signaling. This framework offers new insights into immunometabolic dysregulation and therapeutic strategies in inflammatory, infectious, and neoplastic diseases.

I am a biologist with training in Genetics and Molecular and Cellular Biology, but my path has always been guided by a deep interest in immunology and in understanding how life experiences shape our biology. During my PhD, including a period at Harvard Medical School (McLean Hospital), I began investigating how stress—especially early-life stress—modulates immune function and influences vulnerability to mood disorders. I later continued this line of research as a postdoctoral researcher at Pontifical Catholic University of Rio Grande do Sul (PUCRS), Brazil.

The epithelial, microbial, and immune components of the intestinal barrier coexist in harmony to prevent undesirable inflammatory outcomes and ensure homeostasis in the host. In this review, we outline molecular mechanisms by which T cells regulate intestinal homeostasis and how the ageing-associated dysfunction of T cells could disturb host–microbiota symbiosis and the physical integrity of the intestinal barrier, ultimately driving inflammageing and poor health outcomes. Finally, we propose microbiota- and T cell-based therapeutic interventions aimed at strengthening the intestinal barrier to promote healthier longevity. Namely, we discuss the transplantation of youthful microbiota, the use of designed probiotics, and the adoptive transfer of competent or engineered T cells.

While androgen deprivation is widely used in urological oncology to restrain tumor growth and prevent T cell exhaustion, Lee et al. reveal a striking reversal in glioblastoma. In glioblastoma, androgen loss triggers microglial cytokines, activates the hypothalamic–pituitary–adrenal axis, and induces glucocorticoid-dependent T cell suppression, which accelerates tumor progression.

Katharina Schmack

I am an immunologist with over 15 years of experience in translational biomedical research, specializing in T cell biology, autoimmune diseases, and gastrointestinal cancers. My work explores how immune cells maintain balance, drive inflammation, and regulate epithelial transformation, with a growing focus on immune–microbiome interactions and strategies to therapeutically modulate them. I also earned an Executive MBA to support this translational vision. Beyond research, I am committed to advancing women’s participation in science, promoting gender-responsive medicine in inflammatory bowel disease and colon cancer, and fostering connections between patient associations and key stakeholders.

I am a cancer immunologist and a junior group leader in precision immuno-oncology in Milan, Italy. My work focuses on developing personalized immunotherapy strategies for solid tumors, generating patient-specific tumor-reactive T cells, and investigating how tumors escape immune surveillance. In November 2022, while I was a postdoctoral researcher in Italy, I took parental leave following the birth of my child.

Bioelectric signaling may represent an emerging layer of macrophage communication. This forum discusses how membrane-potential dynamics, ion fluxes, and context-dependent intercellular coupling may coordinate macrophage responses within tissues, highlighting a potential new dimension of immune regulation with broad implications for tissue-level immunity.

Immunity and metabolism are deeply intertwined in maintaining homeostasis. With the recognition of cytosolic dsDNA sensing as an initiator of immune responses, its interface with metabolic rewiring has emerged as a key area of investigation. Focusing on the stimulator of interferon genes adaptor protein, critical for dsDNA-mediated inflammation, we examine the link between lipid metabolism and innate immunity. Adopting an evolutionary perspective and through comparisons with the inflammasome pathway, also specialized in innate immune activation, we explore the conservation of this interface across innate immune systems. We propose that the connection between dsDNA sensing and metabolism could unlock innovative precision medicine strategies for inflammatory diseases.

Pancreatic cancer is a deadly disease defined by an immunosuppressive microenvironment refractory to therapy. Kiemen et al. applied 3D histology, imaging mass cytometry, and spatially resolved DNA sequencing to human pancreata containing early precursors of the disease, revealing heterogeneous and mutation-specific inflammatory niches that are poorly resolved by 2D methods.