- IKKα stabilizes ATG16L1
Decreased ATG16L1 stabilization is associated with increased susceptibility to develop inflammatory bowel diseases. Diamanti et al. identify IKKα as a central upstream kinase of ATG16L1, providing evidence that ATG16L1 stabilization is controlled by phosphorylation downstream of TNF and NOD activation.
- Epidermal Par3 controls melanoma via P-cadherin
Mescher et al. uncover a novel tissue-borne tumor suppression mechanism, engaging polarity proteins in the epithelial microenvironment that prevent malignant outgrowth of neighboring cell types through control of heterologous cell–cell contacts. Moreover, their data support an emerging role of P-cadherin, which is frequently amplified in human carcinoma, as a protumorigenic and proinvasive adhesion molecule, thus placing it as a promising druggable target to disrupt tumor–microenvironment interactions for anticancer therapy.
- LAG-3 and 4-1BB describe dysfunctional TIL
Williams et al. show that 4-BB and LAG-3, previously identified as EGR2 targets from in vitro T cell anergy studies, are sufficient to identify dysfunctional tumor antigen–specific CD8+ T cells in the tumor microenvironment. These markers facilitated detailed transcriptional and phenotypic characterization and provided therapeutic targets for tumor control.
- CD70/CD27 signaling promotes blast stemness in AML
Riether et al. show that CD70/CD27 signaling activates stem cell gene expression programs in acute myeloid leukemia (AML). Blocking the CD70/CD27 interaction inhibits self-renewal and induces differentiation of AML blasts and stem/progenitor cells.
- Hypomorphic ATG16L1 triggers IRE1α-mediated ileitis
Tschurtschenthaler et al. report a Crohn’s disease–like ileitis mediated by IRE1α that develops in mice with intestinal-epithelial Atg16l1 deletion when they age. The authors propose a selective autophagy process involved in the removal of IRE1α clusters during ER stress.
- Regulating TCR hyperresponsiveness in the ZAP-70 W131A mutant mouse
Hsu et al. show that a hypermorphic allele of Zap70, characterized by reduced autoinhibition, is associated with increased TCR signaling and triggers regulatory mechanisms by which negative selection and inhibitory receptors restrain TCR signaling to enforce T cell tolerance.
- Human antiviral T cells in tissues
Using a novel human organ donor tissue resource, Gordon et al. reveal how CMV-specific T cells are distributed and function in multiple sites in the context of viral persistence, revealing new insights into immune control of CMV in the body.
- Ephrin-B1 marks GC and memory precursor B cells
Laidlaw et al. show that Ephrin-B1 is a specific marker of mature germinal center (GC) B cells. Use of Ephrin-B1 allows for the identification of phenotypically distinct GC B cell subsets, including a population that may represent memory precursor B cells.
- T reg cells with a single TCR
Levine et al. investigate the extent to which regulatory T cells with either a monoclonal T cell receptor (TCR) or random TCR repertoire in place of their developmentally selected specificities maintain TCR-dependent gene expression and immunosuppressive function.