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Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like T_PEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.

Using single-molecule tracking of cohesin and CTCF during zebrafish embryogenesis, the molecular kinetics underlying chromatin architecture formation was revealed and gradual emergence of chromatin structure recapitulated by polymer simulations.

Memory T cells are vital responders to skin inflammation, but cell localization and dynamics of exchange with the bloodstream are not clear. Here the authors use parabiosis and intravital microscopy to show that CD4⁺memory T cells equilibrate with the circulation and cluster around hair follicles in response to CCL5-dependent responses to viral infection or contact sensitization.

Long-lived tissue-resident memory T cells (T_RM cells) confer fast, robust protection after pathogen rechallenge. Gebhardt and colleagues show that skin T_RM cells arise from KLRG1^– cells that differentiate in situ in response to IL-15 and TGF-β.

Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.

A laser–plasma accelerator provides proton beams for the precise irradiation of human tumours in a mouse model. This work advances translational research with ultrahigh proton dose rates at laser-driven sources.

A transplantable mouse model of persistent cutaneous melanoma shows that immune-mediated tumour suppression can result in a state of melanoma–immune equilibrium, and that tissue-resident memory T cells are essential drivers of this equilibrium state.

Bedoui and colleagues describe a sequential process of integration of innate and CD40-delivered signals in APCs, which optimizes their capacity to drive antiviral CD8⁺ T cell responses.

Pulsed electron-electron double resonance spectroscopy (PELDOR/DEER) and single-molecule Förster resonance energy transfer spectroscopy (smFRET) are used to determine conformational changes and probe distances in biological macromolecules. Here the authors compare the methods on a large set of samples.

Tissue-resident memory T cells (T_RM cells) protect against recurrent or renewed infection in barrier tissues such as skin and mucosa. A new study sheds light on the clonal origin of T_RM cells and demonstrates a crucial role for tissue-embedded T cell memory in contact hypersensitivity in skin.

Cancer is often associated with mutant transcription factors (TFs) but their functional characterization is challenging. Here, the authors describe a recurrent mutation within TF IRF4 in human lymphomas and they show how it causes a complex switch in TF specificity and functionality.

Visceral adipose tissue contains populations of regulatory T cells that exhibit sexual dimorphism, determined by the surrounding niche, and differ between male and female mice in terms of cell number, phenotype, transcriptional landscape and chromatin accessibility.

Zebrafish larvae can binocularly detect prey objects in order to strike but lack ipsilateral retinotectal fibers for binocular superposition of visual information. Here the authors describe commissural intertectal neurons and show that they are required for the initiation of capture strikes.

Killer T cells were thought to patrol the body unhindered, freely gaining access to sites of infection. But it seems that, at least in some body tissues, helper T cells must pave the way for killer T-cell entry.

Researchers demonstrate a laser-plasma accelerator-driven free-electron laser in a seeded configuration, where control over the radiation wavelength and longitudinal coherence are achieved.

Miz1 is a binding partner of the transcription factor c-Myc and a regulator of cell cycle progression. Wolf et al. show that inactivation of Miz1 in the mouse central nervous system results in neurodegeneration, and find that Miz1 is essential for the transcriptional regulation of autophagic flux.

Plant-associated rhizosphere bacteria produce gramibactin, a cyclic lipodepsipeptide siderophore that tightly binds iron via an unexpected functional group, the N-nitrosohydroxylamine (diazeniumdiolate) moieties of the amino acid graminine.

Amyotrophic Lateral Sclerosis related TDP-43 protein translocates to stress granules with a concomitant reduction in mobility. Here, the authors use single molecule tracking and find a stress-induced reduction in TDP-43 mobility also in the cytoplasm potentially relevant for TDP-43 aggregation.

A method that exploits the double-stranded DNA-targeting capability of the bacterial toxin-derived cytosine deaminase, DddA, can map DNA–protein interactions in bacteria in vivo at genome-wide scale.

T cells can acquire a broad spectrum of differentiation states following activation; certain subtypes of T cells have emerged as key determinants of cancer immunity and response to immunotherapies. Here, Gebhardt, Park and Parish discuss the phenotypic and functional variation of stem-like exhausted CD8⁺ T cells and memory CD8⁺ T cells, and how it contributes to their roles in immune escape and cancer outcome.

The relationship between peripheral and recirculating memory cells remains mostly undefined. Carbone and colleagues present evidence of tissue-resident memory T cells that can provide protective immunity at points of pathogen entry.

Shaping particle beams generated from laser-plasma accelerators is challenging. Here the authors demonstrate an all-optical method to structure the accelerated proton beam by modulating and imprinting the spatial laser profile onto the proton beam.

Mackay, Mueller and colleagues show that tissue-resident memory T cells proliferate in situ in response to local antigen and persist during subsequent antigen encounters.

Noncognate CD8⁺ memory T cells can be rapidly activated by bacteria. Bedoui and colleagues show that this process is specifically dependent on recognition by and activation of the NLRC4 inflammasome.

Yersinia ruckeri is the source of redmouth disease in fish. Here the authors analysed the Yersiniatoxin Afp18 and show that it acts to inhibit RhoA activation by glycosylating a distinct tyrosine residue inducing a signalling incompetent structural conformation.

Multi-proxy core data and model simulations support the presence of temperate rainforests near the South Pole during mid-Cretaceous warmth, indicating very high CO₂ levels and the absence of Antarctic ice.

Gut microbial and metabolite alterations are linked to inflammatory bowel diseases pathogenesis. Here the authors identify functional microbiota signatures that correlate with disease activity by comparing patients with Crohn’s disease undergoing autologous hematopoietic stem cell transplantation who either did not respond to therapy, experienced relapse after remission or maintained remission, and show that these microbial signatures recapitulate disease activity when transferred to mice.

Bedoui and colleagues discuss the naive state of conventional T cells as an actively repressed condition that supports T cell diversity and enables the flexible differentiation of effectors, and also offers a relevant discrimination criterion between innate and adaptive lymphocytes.

CD40 has long been known as a co-stimulatory molecule involved in T cell help for dendritic cells, and thereby as a contributor to CD8⁺ T cell immunity against cancers and infections. However, CD40 signaling drives complex functional responses that can contribute to tumor-specific CD8⁺ T cell responses in unexpected ways.

A new bacterial toxin from pathogen Photorhabdus asymbiotica is now described. The toxin contains a domain with glycosyltransferase activity that modifies a tyrosine residue of Rho GTPases in the host cell, inhibiting Rho activation and interaction with downstream effectors. The second domain is a glutamine deamidase that blocks GTP hydrolysis by Ga_q/11 and Ga_i proteins.

This paper reports the genome sequence of domesticated tomato, a major crop plant, and a draft sequence for its closest wild relative; comparative genomics reveal very little divergence between the two genomes but some important differences with the potato genome, another important food crop in the genus Solanum.

The use of antibodies against tumour necrosis factor (TNF) has markedly improved the treatment of Crohn's disease, but only certain patients respond to therapy. Here, Raja Atreya and colleagues have developed an approach using topical fluorescent antibodies to TNF and confocal laser endomicroscopy to evaluate the expression of transmembrane TNF (mTNF) in the intestinal mucosa of patients with active Crohn's disease in order to identify patients likely to respond to subsequent treatment with the anti-TNF therapy, adalimumab.