Issues

This study describes a Mycn-nGEMM for neuroblastoma. Murine and human neuroblastomas showed profound immunosuppression mediated by PD-L1–expressing, TAMs. Anti–PD-L1 immunotherapy depleted TAMs and inhibited tumor growth, demonstrating the potential for myeloid-targeted immunotherapies to overcome the immuno-inhibitory barriers.

In this study, Gawish et al. show that RNA editing of the actin cross-linker FLNA is similarly regulated in mice and humans and that the targeted induction of edited FLNAR in myeloid cells governs resistance to DSS-induced colitis, revealing its potential in IBD therapy.

Type I IFN signaling contributes to arthritis pathogenesis in obesity through activation and expansion of CD8 T cells in visceral adipose tissue and synovium. Deletion of IFNAR1 in T cells reduces arthritis severity in obese mice.

Lane et al. discover that the lymphatic vasculature is functionally and transcriptionally distinct along the gut. Duodenal lymphatic vessels appear optimized for dietary lipid uptake. Duodenal helminths compromise this property, providing an alternative explanation for worm-induced resistance to weight gain.

TLOs are LN-like structures that are observed in certain inflammatory diseases. Geng et al. demonstrate that S1PR1 activity in the lymphatic vasculature is necessary to prevent TLO formation in the terminal ileum.

During obesity, the bone marrow is dysregulated to overproduce myeloid cells that drive systemic inflammation. Neutrophil migration is a key mediator of this process, and targeting neutrophil movement during obesity or weight loss improves inflammatory and metabolic outcomes.

In this study, we report that microbiota depletion exacerbates acute graft-versus-host disease in the central nervous system, driven by microglial activation and T cell infiltration. Administration of the bacteria-derived metabolite N,N,N-trimethyl-5-aminovaleric acid could rescue both microglial activation and associated neurocognitive deficits.

Current mRNA vaccines have either limited efficacy or severe toxicity. This study highlights that next-generation mRNA vaccines encoding membrane-tethered cytokine adjuvants can generate potent pre-effector cells, offering effective tumor control with reduced toxicity.

Cachexia is a devastating cancer comorbidity that impacts numerous cancer outcomes, including therapeutic efficacy, quality of life, and overall survival. This work describes a novel metabolic pathway/target with clinical implications for the treatment of cachectic pancreatic cancer patients.

Plasmodium falciparum circumsporozoite protein harbors conserved human T cell epitopes that may serve as targets for broad strain-transcending immunity. The findings offer guidance for the design of improved malaria vaccines.