NK cells play a critical role in immune surveillance, yet negative regulators of their maturation and function are poorly characterized. Imianowski et al. show that the transcriptional repressor BACH2 restricts NK cell maturation and anti-tumor function, with implications for immunotherapeutic development.

Valencia et al. show DSTYK, a dual serine/threonine and tyrosine kinase, altered in lung cancer and associated with poor clinical outcome. DSTYK controls cellular processes encompassing cytoprotective autophagy and mitochondrial fitness and its ablation sensitizes cancer cells to T cell–mediated killing.

The authors engineer an anti-PD-1–concealed sIL-15 fusion protein (αPD-1-IL-15-R), eliciting extraordinary antitumor immunity with negligible toxicity. αPD-1-IL-15-R largely expands tumor-specific CD8⁺T for effective tumor rejection through cis-delivery and further controls metastasis.

Neonatal HSV (nHSV) infections cause significant morbidity and mortality. This study demonstrates the efficacy of monoclonal antibody therapy via direct administration and AAV vectored expression. Antibodies administered either maternally or to mouse pups improve survival and time-dependent viral clearance.

Wang et al. analyze memory B cell and antibody responses in SARS-CoV-2 mRNA vaccines to breakthrough infections with Delta or Omicron BA.1 variants. Breakthrough infection after two or three doses of mRNA vaccination was comparable to three doses of vaccination in eliciting broad and potent memory B cells. The findings provide insights on broad and strain-specific memory responses after mRNA vaccination with Wuhan-Hu-1.

Nadkarni et al. show that human endothelial cells (EC) engage both NLRP1 and CARD8 inflammasomes. CARD8 is activated by Coxsackie B3 protease-mediated N-terminal cleavage. Knocking out CARD8 attenuates CVB3 propagation and dampens inflammation in a cellular model of viral myocarditis.

Sleep interruption restructures the epigenome of hematopoietic stem and progenitor cells (HSPCs) and increases their proliferation, priming them for exaggerated inflammatory bursts and reducing hematopoietic clonal diversity through accelerated genetic drift. In humans, sleep restriction alters the HSPC epigenome and activates hematopoiesis.