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Brief Definitive Report
Yuki Honda Keith et al.
Tissue-resident CSF1R-dependent CD169+ macrophages localize deep in the skin. They surround growing tumors and directly suppress their growth independent of T and B cells. CD169+ skin macrophages ingest live tumors, and this phagocytosis is independent of the phosphatidylserine receptor MERTK.
Article
Chenyun Song et al.
This study shows that a secondary microglial expansion center has been identified in fetal brains with oSVZ.
Technical Advances and Resources
Rih-Sheng Huang et al.
We developed a highly efficient nonviral knock-in platform for NK cells, enabling plasmid-based genome editing with up to ∼90% knock-in efficiency and ∼100% recovery. Targeted integration rewires endogenous circuits for context-dependent therapeutic functions and supports GMP-compatible production of CAR-NK cells for clinical translation applications.
Article
Rafael Blanco-Domínguez et al.
Blanco-Domínguez et al. demonstrate that regulatory T cells constrain IFNγ-producing γδ T cells by competing for IL-2, thereby limiting their expansion and anti-tumor function. IL-2Rβγc agonism can overcome this suppression to enhance γδ T cell–mediated tumor control.
Article
Jie Li et al.
The chemokine CCL25 is expressed in the thymus and the small intestine. Li et al. show that thymic epithelial CCL25 facilitates T cell positive selection in the thymic cortex, whereas intestinal epithelial CCL25 promotes nutrient sensing in the small intestine. Epithelial CCL25 directs thymic T cell development and intestinal homeostasis in a tissue-specific paracrine manner.
Article
Megumi Tatematsu et al.
CNOT3 promotes the degradation of Tbx21 and Rorc mRNAs through Roquin and ZFP36L1 in ILC2 cells, thereby inhibiting type 1 and type 3 plasticity and maintaining ILC2 function.
Article
Shibo Liu et al.
Liu et al. develop PRECISE-seq, a single-cell platform linking TCR specificity and avidity to T cell phenotypes in vivo. They reveal that high-potency antiviral T cells become exhausted, while tumor-reactive CD8+ T cells acquire a regulatory Ly49+ state that is restrained by PD-1 blockade, resulting in effector revival within tumors.
Journal of Experimental Medicine Cover Image for Volume 223, Issue 5
Current Issue
Volume 223,
Issue 5,
4 May 2026

Reviews & Opinions

Insights
Rundi Zhu et al.
In this issue of JEM, Liu et al. report PRECISE-seq, a proximity labeling platform that integrates T cell receptor specificity, functional potency, and cellular phenotype at a single-cell resolution. Using this approach, they identify an immunosuppressive Ly49+ T cell state within tumors that is alleviated by PD-1 blockade.
Insights
Sangwoo Park, Marcela V. Maus
Repeated tumor contact leaves more behind than simple CAR-T exhaustion. This study shows that chronic antigen exposure impairs a Rab5-dependent endocytic program, allowing trogocytosed antigen to accumulate, functional CAR to decline, and fratricide to increase.
Insights
Mauricio Guzmán et al.
In this issue, Luff et al. show that cell-intrinsic signals from TACI drive marginal zone B cell development from T2 B cells through a mechanism involving activation of the PI3K–AKT pathway and inhibition of the FOXO1-KLF2 axis.

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