Volume 25 Issue 5, May 2024

The microbiome is known to affect antitumor immune responses, but how this occurs is unclear. Rhamnose-rich polysaccharides (RHP) from a commensal strain of Lactiplantibacillus plantarum have now been shown to induce iron sequestration by tumor macrophages, thereby limiting tumor growth and promoting antitumor immunity.

Age is the single greatest risk factor driving mortality after encounter with SARS-CoV-2. A new study shows that the composition of nasal epithelial cells varies across ages, facilitating SARS-CoV-2 growth and spread in older people.

Specialized T cell effector functions depend upon pre-established chromatin state. Cooperativity among PU.1, RUNX1 and BCL11B directs SWI–SNF complex recruitment to carry out chromatin priming at T cell effector loci during early thymic development.

MEF2C is a transcription factor that has known functions in a variety of cell types, but it has not yet been ascribed a role in natural killer cells. Data now show that MEF2C promotes the functional responses of human and murine natural killer cells by controlling their metabolic programs.

Inflammatory memory cues initiated by neutrophils and bone marrow stroma suggest potential therapeutic targets for the treatment of multiple myeloma.

We report two patients with biallelic SHARPIN deficiency, which manifests with autoinflammation and B cell immunodeficiency and is phenotypically distinct from Sharpin deficiency in mice. In one patient, there was a significant shift from pro-survival signaling to cell-death signaling in fibroblasts and lymphoblasts induced by members of the TNF cytokine superfamily, accounting for the autoinflammation and immunodeficiency. Targeted therapy with TNF inhibitors had a dramatic beneficial effect.

In this study, we use a transcriptomic approach as a starting point to explore the heterogeneity of human GATA3-expressing lymphocytes across different tissues and disease contexts. We identify, characterize and functionally validate an abundant progenitor-like memory T cell population with the potential to sustain pathogenic T_H2 cell inflammation.

The intestinal immune response is tightly controlled to limit inflammation, largely by the cytokine IL-10, which prevents colitis. We report that the transcription factors c-MAF and BLIMP-1 induced IL-10 in T cells in the colon, but also acted to negatively regulate distinct cytokine pathways to restrict pathobiont-induced colitis.

The transient expression of CD61 and its unconventional pairing with CD103 at the immune synapse enhances T cell receptor signaling, improves anti-tumor cytotoxicity and mitigates tumor growth. Clinically, CD61⁺ tumor infiltrating lymphocytes (TILs) exhibit enhanced effector functions and show limited cellular exhaustion.

Homeostatic immune cells remain perpetually vigilant against pathogens. We found that baseline JAK–STAT signaling supports the characteristic transcriptional and epigenetic state of homeostatic T cells and macrophages in mice. JAK–STAT signaling under homeostatic conditions was driven by signals from healthy tissue and did not require external immune stimuli.

In this Review, the authors analyze evidence for autoimmunity against components of antimicrobial immunity, metaphorically represented by the mythical ouroboros snake eating its own tail.

Here the authors show how the liver affects the immune response to pancreatic ductal adenocarcinoma and that cancer immunity and survival outcomes after surgery might be bolstered by therapeutic intervention on hepatocyte release of serum amyloid A proteins.

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

Here the authors identify the transcription factor MEF2C as essential for human NK cell function and viral immunity in mice and humans. This control is exerted via regulation of lipid metabolism, and deficiency in MEF2C can be overcome by oleic acid supplementation.

Here the authors show that a heteropolysaccharide from a commensal bacteria commonly found in the Korean food kimchi is able to bolster antitumor immune responses by instructing tumor-associated macrophages to release lipocalin-2, which sequesters iron away from tumor cells contributing to the immune response to attack these cells.

Here the authors show that sepsis and its resolution alter cancer susceptibility by epigenetically altering resident macrophages resulting in retention of T cells that increase antitumoral immunity.

Cupedo and colleagues show that neutrophils promote a tumor-supportive microenvironment via a self-amplifying interaction between neutrophils and bone marrow stromal cells. This scenario creates a promyeloma niche that is difficult to treat despite targeted therapies directed at the myeloma cells.

CD103⁺ T cells are associated with control over tumors but how this is mediated is unclear. Here the authors show that CD61 colocalizes and functionally combines with CD103 in the T cell synaptic response to promote antitumor T cell responses.

Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8⁺ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.

Koh et al. show that loci active in differentiated effector T cells are poised in early T precursors before the expression of T cell antigen receptors in a manner dependent on the chromatin remodeling complex mammalian SWItch/Sucrose Non-Fermentable and the PU.1–RUNX1 and BCL11B–RUNX1 complexes.

Here the authors show a mechanism by which mitochondrial electron transport and ROS contribute to the differentiation and function of regulatory B cells in the context of systemic lupus erythematosus.

In this Resource, the authors integrate multiomics data to show the effect of the transcription factors Blimp-1 and c-Maf on IL-10 and type 1 and 17 responses, which together protect against pathobiont-induced colitis.

Kratchmarov et al. identified a GATA3⁺ T_H2 population that expresses the transcription factors TCF1 and LEF1 and sustains type 2 inflammation in tissues over a human lifetime, despite chronic antigen exposure.

In this Resource paper, the authors integrate T cell antigen receptor, B cell antigen receptor and exome sequencing comparing early and metastatic breast cancer in humans, showing how the immune response and tumors coevolve.