Billiet et al. identify the post-thymic progeny of the agonist-selected CD10⁺ PD-1⁺ precursors in humans based on shared characteristics of the T cell receptor repertoire and the transcriptome. This lineage represents a well-defined but heterogeneous, unconventional TCRαβ⁺ lineage mostly confined within the CD8⁺ Helios⁺ T cells.

Qin and colleagues develop a genome-editing tool characterized by the versatility of prime editors and unconstrained PAM requirement of SpRY. In vivo gene correction is successfully implemented in the mouse model of Pde6b-associated retinitis pigmentosa, leading to substantial functional rescue of vision.

Extracellular nucleases of the DNASE1 family are conserved in vertebrates, yet their physiological function remains unclear. This study shows that DNASE1 and its homolog DNASE1L3 jointly facilitate resistance to systemic infection with Staphylococcus aureus by digesting bacterial biofilms.

Abdulla et al. show that the LMO2 transcription factor, a key driver of human T-lymphoblastic leukemia, inhibits thymocyte competition in a transgenic mouse model and that this enables LMO2 to promote T-lymphoblastic leukemia.

In the DONIMI trial, a baseline IFN-γ signature enables prospective selection of patients who can benefit from anti-PD-1 monotherapy. In contrast to results of our murine melanoma model, domatinostat (a class I HDAC inhibitor) does not add benefit to neoadjuvant anti-PD-1 ± anti-CTLA-4 in patients.

Sawyer et al. reveal the diversity of human tuberculosis granulomas by profiling 726 individual lesions by multiplex imaging. As well as necrotizing lesions, they identify four distinct lesion types that organize in a histopathological superstructure around necrotic granulomas.

Thouenon et al. describe a novel primary immunodeficiency associated with defective plasma cell differentiation. They reveal that an amino acid exchange located within the interferon activation domain of IRF4 downregulates transcription on ISRE sites because of altered protein interaction.