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Cangkrama et al. show that tumor cells from various cancer types use the mitochondrial trafficking protein MIRO2 and nanotubes to transfer mitochondria into surrounding fibroblasts, thereby inducing cancer-associated fibroblast differentiation and subsequent tumor growth.

IL-1 is important in the immune response to Candida albicans. Here the authors show that the protective role of IL-1 in a fatal systemic murine model of infection involves metabolic modulation including inhibition of oxidative phosphorylation and hypoxia via signaling in non-hematopoietic cells.

A transient in vivo prime editing strategy is developed for the liver by delivering the prime editor as mRNA encapsulated in LNP.

Overabundance of apolipoprotein C3 (ApoC3) is associated with atherosclerosis. Speer and colleagues demonstrate that ApoC3 activates the NLRP3 inflammasome via a non-canonical pathway contributing to inflammation and development of atherosclerosis.

This work introduces engineered TnpBmax proteins with enhanced efficiency and an expanded targeting range. By leveraging an extensive dataset on editing efficiencies, it also integrates a deep learning model to predict guide RNA activity.

Details of the ontogeny of alveolar macrophages remain unclear. Kopf and colleagues show that fetal monocytes give rise to alveolar macrophages in a manner dependent on the nuclear receptor PPAR-γ and the cytokine GM-CSF.

Can erasing bad memories relieve pain? Stegemann et al. uncover the cellular basis of fear–pain interactions, reporting that fear potentiates pain via memories encoded in prefrontal engrams. Blocking these memory traces reduces chronic pain in mice.

VEGF-C induced lymphangiogenesis combined with immunotherapy approaches can promote anti-tumor immune responses. Here the authors report that lymphaticderived oxysterols promote anti-tumor immunity and response to immunotherapy in preclinical melanoma models

Thioredoxin (Trx), Trx reductase, Txnip and NADPH together comprise the Trx system. Here the authors make a T cell-specific thioredoxin reductase-1 knockout mouse to show how this system reprograms cellular metabolism to enable T cell development, proliferation and responses.

Chronic inflammation is a fundamental aspect of metabolic disorders such as atherosclerosis. Freigang and colleagues report that fatty acids are potent inducers of IL-1α, which drives vascular inflammation.

Pancreatic cancer is characterized by an immunosuppressive microenvironment, leading to immune evasion. Here, based on in vitro and in vivo CRISPR screens, the authors identify Rnf31 and Vps4b as drivers of immune escape, showing that loss of their function leads to an increase in T cell-mediated killing and reduced tumor growth in preclinical pancreatic cancer models.

Hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality.

Cytokines — key instigators and regulators of immune responses — hold potential as targets for new therapeutic strategies. Here, Kopf and colleagues highlight some of the most effective and promising cytokine targets that have been linked to inflammatory diseases in preclinical and clinical studies and discuss some of the issues facing the development of cytokine-targeted drugs.

Group 2 innate lymphoid cells (ILC2s) are a component of type 2 immune response recently described to be involved in the regulation of anti-tumor immune responses. Here, the authors show that the expression of the peroxisome proliferator-activated receptor γ (PPAPγ) in human and mouse ILC2 sustains type-2 cytokines secretion and support their pro-tumorigenic role in preclinical cancer models.

Two opposite processes control the size of the protective root cap in Arabidopsis during growth: cell division and shedding of old cells layers (sloughing). Here, the authors show the role of a receptor–ligand pair in this regulation.

IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.

The lungs hosts their own unique populations of macrophages and dendritic cells. In this Focus Review, Kopf, Schneider and Nobs discuss the development and maintenance of these populations in the lungs.

The signaling receptor Notch is required for the generation of marginal zone B cells. Hammad and colleagues show that Notch signaling activates the kinase Taok3 and surface expression of the metalloproteinase ADAM10, which commits transitional B cells to the marginal zone B cell fate.

Determining TCR specificity represents a formidable technical barrier to the harnessing of T cell function. Kisielow and colleagues describe a novel platform for efficient determination of TCR specificities in a variety of infectious and cancer settings and in both human systems and mouse systems.

Metabolic pathways play a central role in determining the fate and function of immune cells, and cellular activation induces profound changes in their oxidation–reduction (redox) system. Here, Muri and Kopf examine the crosstalk between metabolic and redox pathways and discuss their role in the proliferation, survival and function in T cells, B cells and macrophages.

Systemic exposure to dietary and microbial components induces long-lasting epigenetic and metabolic changes in myeloid precursor cells, which results in enhanced proinflammatory and anti-microbial responses of mononuclear phagocytes after challenge with related or unrelated stimuli.

Recent data indicate that chemokines have a role in regulating dendritic-cell maturation. In this Opinion article it is proposed that this ensures that dendritic cells migrating to the lymph node arrive in a fully mature state that is optimal for T-cell priming.

In this Review, Dai, Stockwell, Kroemer, Tang and colleagues offer a comprehensive discussion of the molecular regulation of ferroptosis and highlight how this may be potentially leveraged for therapeutic benefit for disease treatment.