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TCR microcluster signaling occurs in cognate T cells after they encounter antigen-presenting cells. Krummel and colleagues show that immune synapses are motile as microclusters coalesce after the actin depolymerization that occurs during T cell movement.

CD8⁺ T cell are primed via recognition of cognate peptides presented by APCs. Krummel and colleagues show that optimal CD8⁺ T cell differentiation then occurs via T cell–T cell interactions dependent on the integrin LFA-1.

Lymphocytes must rapidly scan lymph nodes for cognate antigens. Krummel and colleagues show that myosin IIA acts to optimize cell motility by regulating cell contacts through lymph node stromal environments.

T cells proliferate in response to cues provided by antigen-presenting cells or high concentrations of cytokines. Krummel and colleagues reveal a distinct requirement for the cytoskeletal protein septin 7 for cytokine-driven bystander T cell proliferation.

Cross-talk between innate immune cells helps to enhance the antitumor T cell response during checkpoint blockade therapy.

Patients with mild COVID-19 show a pattern of interferon-stimulated gene (ISG) expression across all major cell types, but in patients with severe disease, antibodies block the production of these ISG-expressing cells.

Taking lessons from 'search theory', which is based on migration patterns of animals searching for prey, for example, Krummel and colleagues discuss the intrinsic and extrinsic forces that influence T cell motility patterns as the cell searches for antigen in lymphoid and non-lymphoid tissues.

Septins are cytoskeletal proteins that form a ring at the cytokinetic furrow. Now an analogous 'molecular corset' of septins is found to be required for T lymphocyte migration.

Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

In this work, authors assess airway microbiome dynamics to show bacterial pneumonia in critically ill COVID-19 patients is significantly associated with death, corticosteroid treatment, disruption of the lung microbiome and a distinct pulmonary host response.

Multiphoton microscopy requires precise increases in excitation power with imaging depth to generate contrast without damaging the sample. Here the authors show how an adaptive illumination function can be learned from the sample’s shape and used for in vivo imaging of whole lymph nodes.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

ZipSeq uses patterned illumination and photocaged oligonucleotides to serially print barcodes onto live, intact tissues for spatially mapping single cell transcriptomes.

Host immunity requires cytotoxic lymphocytes that are able to move toward their targets but are also able to stop after identifying target cells and then establish stable cell-cell contact. A new study shows that separate phosphorylation sites in HS1, an actin cytoskeleton–remodeling factor, can regulate both processes.

A study describes the metabolic adaptations supporting differentiation, survival and function of tissue-resident memory CD8⁺ T cells and how to leverage them to enhance immunity against pathogens and tumours.

Fast, two-photon intravital imaging of a mechanically stabilized and physiologically intact preparation of the mouse lung is reported. It is used to monitor immune cells in the lung under normal and injured conditions.

Dexamethasone has been used in the treatment of critically ill COVID-19 patients. Here the authors apply transcriptomics to investigate the effects of dexamethasone treatment in COVID-19 patients, and show both systemic and compartment-specific effects.

Tracing the fate of circulating tumour cells by intravital two-photon lung imaging shows that tumours produce microparticles as they arrive and these migrate along the lung vasculature and are mostly taken up by interstitial myeloid cells, in a process that contributes to metastatic seeding; a minor subset of microparticles is engulfed by conventional dendritic cells, which are thought to contribute to the initiation of an anti-tumour immune response in lung-draining lymph nodes.

Atmospheric data and chemical-transport modelling show that CFC-11 emissions from eastern China have again decreased, after increasing in 2013–2017, and a delay in ozone-layer recovery has probably been avoided.

Assessing metabolic activity within single cells rather than at a population level has a number of advantages. Here, the authors use a flow and mass cytometry based approach that assess the metabolic differences between populations of human immune stimulatory and tolerogenic dendritic cells.

Atmospheric concentration measurements at remote sites around the world reveal an accelerated decline in the global mean CFC-11 concentration during 2018 and 2019, reversing recent trends and building confidence in the timely recovery of the stratospheric ozone layer.

Atmospheric measurements show that China’s emissions of the potent greenhouse gas, sulfur hexafluoride, grew rapidly between 2011 and 2021. This rise could offset some of China’s progress towards its greenhouse gas emission reduction goal.

Dichloromethane (CH₂Cl₂) is an unregulated ozone depleting substance whose emissions have strongly increased in recent years. Here, the authors show that rising emissions of dichloromethane in China between 2011 and 2019 can explain much of this global increase.

Atmospheric levels of chloroform increased after 2010, as a result of emissions in eastern China, according to analyses of measurements and inverse modelling.

To demonstrate the long-range effects of CD8⁺ T cell–secreted interferon-γ on bystander tumor cells, two studies now use mosaic models of antigen loss in tumors combined with intravital imaging. Factors that influence the length scale of diffusible signals could shape disease progression in cancer and autoimmunity.

The imaging of tissues and organs as it is now practiced will seem primitive in the coming decade, yet use of this technology will define the origin of emergent activities and drive an era of system integration.

The inhibitory protein PD-1 is expressed on activated T cells. Fife and colleagues find that interactions between PD-1 and its ligand PD-1L are needed to maintain tolerance and prevent interactions between tolerized T cells and dendritic cells.

In this Perspective, the authors suggest that different tumour microenvironments have ‘archetypal’ qualities across all cancers — characteristic and repeating collections of cells and gene-expression profiles at the level of the bulk tumour. They propose the existence of 12 dominant immune archetypes.

Medulloblastoma is the most common brain tumour in children; using exome sequencing of tumour samples the authors show that these cancers have low mutation rates and identify 12 significantly mutated genes, among them the gene encoding RNA helicase DDX3X.

Direct imaging of the lung microcirculation in mice indicates that it is a major site of mature platelet production from megakaryocytes.

The tumor immune microenvironment influences tumor progression and response to immunotherapy; its further characterization will improve therapeutic outcome.

Eosinophil recruitment to the lung and intestine is regulated by type-2-innate-lymphoid-cell-derived IL-5 and IL-13; IL-5 is shown to be induced by the neuropeptide vasoactive intestinal peptide, which is known to coordinate pancreatic secretion with smooth muscle relaxation in response to feeding.

In this Review, Smyth and colleagues provide an overview of recent advances in NK cell biology and discuss the progress and problems of NK cell–based cancer immunotherapies.

There is growing interest in harnessing dendritic cells for cancer immunotherapy. Here the authors describe the roles of dendritic cells in the tumour microenvironment and the different strategies that are being developed to target these cells in the clinic.