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Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

A comprehensive characterisation of the proteomic landscape of lymphoid malignancies remains elusive. Here, high-throughput proteomic profiling of 6,412 circulating proteins identifies potential risk stratification markers.

Urban blue spaces, such as lakes and rivers, play growing roles in cities but are historically vital for providing food. Focusing on four Indian cities, this study finds diverse blue foraging practices most practiced by elderly women, especially among the most disadvantaged groups.

Borsa et al. show that asymmetric T cell division after activation requires autophagy to promote mitochondrial turnover, with T cells inheriting older mitochondria showing decreased degradation, reduced memory potential and altered metabolism.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

The NeoRHEA trial showed that treatment with palbociclib and endocrine therapy decreases T cell proliferation and the presence of tissue-resident memory T cells. These results are important for the development of CDK4 selective inhibitors.

Tumour-reactive CD8⁺ T cells are enriched in functional clusters with tumour cells and/or antigen-presenting cells and can be isolated and expanded from clinical samples.

COVID-19 severity is linked to microthrombus formation. Here, using an in vivo two-photon imaging technique in mice and human scRNA-Seq data, the authors show increased adhesion molecules on vascular neutrophils leading to platelet aggregation and reduced lung perfusion.

CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.

Mechanisms of clonal evolution in myeloid neoplasms remain incompletely understood. Darwinian theory predicts that the (micro)environment of clone-propagating stem cells may contribute to clonal selection. Here, authors provide data fitting this model, establishing a relationship between stromal niche inflammation, inflammatory stress in HSPCs, clonal resistance and leukemic evolution in human myelodysplastic syndrome.

This study develops a distributive justice framework for allocating subnational carbon budgets. Applying it to the EU, it reveals substantial within-country differences in production- and consumption-based allocations, with implications for designing equitable net-zero pathways.

Independent smallholder farmers without exclusive contracts with specific mills were underrepresented at certified palm oil mills, and they contributed one-third of regional oil palm production, according to an analysis using a conceptual model of market participation and palm oil data.

How and when memory T cells emerge remains unresolved. Chang and colleagues use single-cell analyses to identify gene-expression signatures predictive of the eventual fates of individual CD8⁺ T cells during immune responses in vivo.

New fossil fuel investments may become stranded if demand for fossil fuel declines due to technological change. This could amount to a discounted global wealth loss of US$1–4 trillion, with the negative impact for producer countries amplified by climate mitigation policies of consumer countries.

Combination radiotherapy (RT) + αPD-L1 enhances tumor control via a tumor-draining lymph node (TdLN)-derived CD8+ PD-1+ TCF-1+ T cells. RT + αPD-L1 induces a novel LY6A+ subset in the TdLN that migrates to the tumor and differentiates into effectors.

Akincilar, Fidan et al. report a conserved role for telomerase reverse transcriptase in regulating inflammation via the cGAS–STING nucleic acid-sensing pathway in myeloid cells, independent of its telomerase activity.

Phenotypic markers that overlap between ILC1 and NK populations have impacted the robust and specific analysis of these immune cell populations. Employing scRNA sequencing here the authors identify CD127⁺ CD94⁺ innate lymphoid cells that express granulysin and perforin and are expanded in patients with Crohn’s disease.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

Patients with classic Hodgkin lymphoma (cHL) respond well to PD-1 blockade, but the underlying cellular insights are still lacking. Here, the authors use single-cell transcriptome and spatial analyses to identify distinct circulating and tumor-infiltrating CD4⁺ T cell, B cell and IL1β⁺ monocyte/macrophage features associated with response to PD-1 blockade in cHL.

Factors governing T cell homeostasis are poorly defined. Hedrick and colleagues find that the transcription factor Foxo1 maintains the homeostasis of naive T cells by regulating genes involved in T cell trafficking and survival.

Regulating the balance between T_H17 cells that drive autoimmune inflammation and nonpathogenic T_H17 cells is critical for limiting autoimmune pathology. Here, the authors extensively characterize these two cell states at the transcriptomic and epigenetic levels and show how BACH2 is protective in this context.

Single-cell multi-omic analysis of 300,000 cells from 29 patients representing peripheral immune cells and colon mucosal immune, epithelial and mesenchymal cells reveals crosstalk between circulating and tissue-resident immune cells with epithelial cells in checkpoint inhibitor colitis and identifies potential therapeutic targets.

Cui and colleagues identify the chromatin organizer protein SATB1 as a critical regulator of quiescence in stem-like progenitor CD8⁺ T cells that arise during chronic viral infection and cancer.

The authors identified a protective genetic allele associated with lower PU.1 (SPI1) expression in myeloid cells by conducting a genome-wide scan of Alzheimer's disease (AD). PU.1 binds the promoters of AD-associated genes (e.g., CD33, MS4A4A & MS4A6A, TYROBP) and modulates their expression, suggesting it may reduce AD risk by regulating myeloid cell gene expression.

Combinatorial experimental and bioinformatics methods can be used to analyse function and specificity of CD8 T cells. Here the authors propose a multiomic analysis framework Antigen-TCR Pairing and Multiomic Analysis of T cell (APMAT) to relate TCR specificity to transcriptomic phenotype indicating associations with physicochemical features.

Understanding the immunological underpinnings of long-term survival in cancer is of high interest. Here, authors dissect the immune parameters of multiple myeloma long-term survivors following a single line of therapy longitudinally, and find sustained changes, including inflammation and impaired immune function.

Here, the authors show that deletion of Pglyrp1 promotes antitumor immunity owing to its inhibitory function in CD8⁺ T cells and that targeting it can inhibit development of autoimmune neuroinflammation. These findings indicate that PGLYRP1 might be a target for immunotherapy.

Although individual genes that distinguish tumor-reactive CD8+ T cells from bystander T cells in tumors have been described, a functionally meaningful integrative signature has not been established. Here authors show that mutation-associated neoantigen-specific CD8+ tumor-infiltrating lymphocytes can be recognized by MANAscore, an algorithm that uses weighted expression levels of CXCL13, ENTPD1 and IL7R in single-cell RNAseq datasets of lung cancer and melanoma patients as input.

Schattgen et al. profiled the subsets and clonality of CD4⁺ T_FH cells in the blood and lymph nodes of human volunteers who received two influenza vaccines 1 year apart to characterize their dynamics and clonal evolution over 2 years.

Using CRISPR-guided editing, Liesenfelder et al. modify DNA methylation at epigenetic clock sites, which evokes genome-wide age-associated epigenetic modifications. Their findings suggest age-associated DNA methylation changes can be coherently modified within an epigenetic network.

Here the authors use single cell profiling of T cells across the human lifespan to show that a suboptimal TCR shift in T cells as we enter older age results in a molecular signature that resembles that of T cells from newborns and children.

Together with the fatty-acid-binding protein  FABP5, the cytoskeletal organizer TAGLN2 is an essential factor for fatty acid uptake, mitochondrial respiration and anticancer function in CD8⁺ T cells.

Petroni et al. report that the infiltration of IL-17A-secreting γδ T cells in the tumor microenvironment coupled with the accumulation of immunosuppressive macrophages is associated with resistance to CDK4/CDK6 inhibition in HR⁺HER2⁻ breast cancer.

The role of therapy in shaping the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) remains to be explored. Here, the authors perform single-cell RNA sequencing in PDAC samples before and after chemotherapy and suggest that chemotherapy may promote resistance to immunotherapy.

Activated B cells and T cells accumulate within joints of patients with rheumatoid arthritis. Here, the authors use single-cell transcriptome and repertoire profiling to identify clonally expanded synovial B cells and T cells and define their phenotypes and predicted cell-cell interactions.

The number of ligand binding sites in the dopamine transporter is enigmatic due to conflicting data from structures and molecular pharmacology. Here, force spectra reveal the position and dynamics of a previously invisible transient site.

Here, the authors show that CD8⁺ T cells egress from tumors via lymphatic vessels in a CXCL12/CXCR4-dependent manner. High-affinity antigen encounter inhibits CXCR4 and increases retention, while no encounter or weak affinity directs T cell exit to limit local tumor control.

Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

Personalized neoantigen vaccination in patients with melanoma elicits durable and specific memory T cell clones that have cytotoxic gene signatures and can diversify to include nonvaccine neoantigen specificities.

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

Tumour-derived prostaglandin E₂, signaling through its receptors EP₂ and EP₄, is shown to restrain the responses of tumour-infiltrating stem-like TCF1⁺CD8⁺ T lymphocytes, and modulation of T cell EP₂ and EP₄ can restore anticancer immunity.

The molecular mechanisms underlying lymph-node metastasis in head and neck squamous-cell carcinoma remain to be investigated. Here, the authors perform single-cell RNA sequencing of cancer cells and CD8 + T cells and suggest potential mechanisms of immune evasion during early metastasis.