Tumor-initiating cells (TICs) are particularly efficient at evading detection and elimination by the human immune system. Recent data from Yang and collaborators demonstrate that – at least in preclinical hepatocellular carcinoma models – the immunological privilege of CD49f+ TICs can be limited by targeting CD155, resulting in restored sensitivity to immune checkpoint inhibitors.

When B cells engage in an immune response, metabolic reprogramming is key to meeting cellular energetic and biosynthetic demands. Epstein–Barr virus (EBV) is a highly prevalent gamma-herpesvirus, latently infecting B cells for the human host’s lifetime. By hijacking signaling pathways of T cell-dependent humoral immunity, EBV activates B cells in a T cell-independent manner, forcing lymphoblastoid transformation. Interlinked with this coercion of signaling pathways, EBV has also evolved strategies to manipulate B cell metabolism. In this opinion article we integrate recent findings from studies of B cell metabolic reprogramming after EBV infection and during antigen-specific activation, respectively. We hypothesize that defining EBV host-cell metabolic vulnerabilities that differ from pathways required for B cell immunity might uncover novel therapeutic targets against EBV-related diseases.

Laboratory mice housed under specific pathogen–free (SPF) conditions are the standard model in biomedical research. However, experiments with a particular inbred mouse strain performed in different laboratories often yield inconsistent or conflicting data due to housing-specific variations in the composition and diversity of SPF microbiota. These variations affect immune and nonimmune cell functions, leading to systemic physiological changes. Consequently, microbiota-dependent inconsistencies have raised general doubts regarding the suitability of mice as model organisms. Since stability positively correlates with biological diversity, we postulate that increasing species diversity can improve microbiota stability and mouse physiology, enhancing robustness, reproducibility, and experimental validity. Similar to the generation of inbred mouse strains in the last century, we suggest a worldwide initiative to define a transplantable ‘wild’ microbiota that stably colonizes mice irrespectiv

Biomolecular condensates are membraneless organelles formed through liquid–liquid phase separation. Innate immunity is essential to host defense against infections, but pathogens also harbor sophisticated mechanisms to evade host defense. The formation of biomolecular condensates emerges as a key biophysical mechanism in host–pathogen interactions, playing pivotal roles in regulating immune responses and pathogen life cycles within the host. In this review we summarize recent advances in our understanding of how biomolecular condensates remodel membrane-bound organelles, influence infection-induced cell death, and are hijacked by pathogens for survival, as well as how they modulate mammalian innate immunity. We discuss the implications of dysregulated formation of biomolecular condensates during host–pathogen interactions and infectious diseases and propose future directions for developing potential treatments against such infections.

Gopee and colleagues’ recent analyses of diverse high-dimensional datasets of prenatal and adult skin, together with data from complex skin organoids, uncover the important contributions of macrophages in modulating prenatal skin development, scarless wound healing, and angiogenesis. These findings identify a role for skin immune cells in tissue development.

Chronic antigen exposure is frequently associated with T cell exhaustion. In a recent study, Aljobaily et al. show that pancreatic islet-infiltrating CD4+ T cells in mouse autoimmune diabetes may circumvent exhaustion by preserving TCF1 expression. Continuous recruitment of epigenetically pre-programmed CD62L+ CD4+ T cells seems to sustain the local autoimmune response.

In the battle against cancer, researchers are exploring the use of engineered bacteria as living medicines. Redenti and colleagues demonstrate that Escherichia coli Nissle 1917 (EcN) can be engineered to deliver cancer neoantigen payloads, stimulating antigen-specific CD4+ and CD8+ T cells and mediating antitumor immunity in preclinical models of colorectal cancer and melanoma.

The recent discovery by Lu and colleagues of Tomasiella immunophila, a bacterium that degrades IgA, offers insights into microbial influences on mucosal immunity and evolutionary immune trade-offs. By modulating IgA titers, T. immunophila influences the dynamic interactions and balance between the host and pathogen. This has implications for immune health, microbiome research, and therapeutics.

The polycomb repressive complex 2 (PRC2) is an established therapeutic target in cancer. PRC2 catalyzes methylation of histone H3 at lysine 27 (H3K27me3) and is known for maintaining eukaryote cell identity. Recent discoveries show that modulation of PRC2 not only impacts cell differentiation and tumor growth but also has immunomodulatory properties. Here, we integrate multiple immunological fields to understand PRC2 and its subunits in epigenetic canonical regulation and non-canonical mechanisms within innate immunity. We discuss how PRC2 regulates hematopoietic stem cell proliferation, myeloid cell differentiation, and shapes innate immune responses. The PRC2 catalytic domain EZH2 is upregulated in various human inflammatory diseases and its deletion or inhibition in experimental mouse models can reduce disease severity, emphasizing its importance in regulating inflammation.