Biology subjects

Taylor, G. S.

Publications and source records attributed to Taylor, G. S..

6 recordsLinked to original sources

bioRxiv2026

Loss of systemic anti-viral immunity and LMP1-driven suppressive myeloid tumour niches converge to shape the immunobiology of EBV+ diffuse large B-cell lymphoma

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBVDLBCL) is an aggressive lymphoma with poor outcomes and an incompletely understood pathogenesis, frequently attributed to immunosenescence. However, its occurrence across all age groups suggests alternative mechanisms. Here, we integrate functional profiling of peripheral antiviral T-cell immunity with high-dimensional spatial proteomics and mechanistic in vitro modelling to define the immunological landscape of EBVDLBCL. We show that both EBV and EBV-DLBCL patients exhibit broad impairments in antiviral T-cell responses compared with healthy controls, affecting latent and lytic EBV antigens as well as non-EBV viral targets, with deficits most pronounced in EBV patients. Spatial proteomic analysis revealed that EBVDLBCL harbours a profoundly immunosuppressive tumour microenvironment characterised by relative loss of intratumoural CD8 T cells, expansion of PD-1 regulatory and exhausted T-cell populations, and dense aggregates of PD-L1/IDO1 macrophages. Compared with EBV classical Hodgkin lymphoma and infectious mononucleosis, EBV DLBCL displayed the most marked macrophage-associated immunosuppressive signature and the lowest T-cell density. Suppressive myeloid niches were preferentially enriched around LMP1-expressing tumour cells, a feature not observed in the other EBV-associated conditions. Together, these findings indicate that EBVDLBCL is driven by the convergence of systemic antiviral immune dysfunction and an LMP1-dependent suppressive tumour microenvironment.

cancer biology↗

bioRxiv2025

The spatial landscape of infectious mononucleosis tonsils

Primary Epstein-Barr virus (EBV) infection remains incompletely understood, particularly in relation to the nature of in vivo latency patterns and their influence on the immune microenvironment. Here, we present the first multiomic single-cell spatial atlas of palatine tonsils from individuals with infectious mononucleosis (IM). We identify rare EBV infection of epithelial cells, challenging the prevailing assumption that primary infection is restricted to B- and T-cells. Moreover, our detailed analysis suggests a spatiotemporal transition of EBV latency programs, with distinct viral gene expression patterns corresponding to specific tissue microenvironments-a dynamic process previously inferred but not directly mapped in human tissues. We found that cells expressing the EBV-encoded protein LMP1 form an immunosuppressive niche that is rich in IDO1+PDL1+ macrophages and relatively depleted of T-cells. Furthermore, the T-cells that do infiltrate LMP1+ regions exhibit signatures consistent with an activated and cytotoxic phenotype, providing new insights into how LMP1 shapes immune evasion. Taken together, our data redefine the spatial and functional organisation of primary EBV infection, integrating latency plasticity, epithelial tropism, and microenvironmental immunosuppression into a unified framework, as well as providing a data-rich framework for understanding viral persistence and immune evasion.

immunology↗

bioRxiv2025

CellMAPS: A no-code model-based customisable multiplex image analysis workflow

Although multiplex imaging allows simultaneous mapping of complex tissue architectures and cellular phenotypes, the dearth of user-friendly robust image analysis workflows remains a significant limitation to its widespread use, restricting multiplex imaging to laboratories with image analysis expertise. Here, we introduce a no-code model-based customisable suite, CellMAPS, which allows both image processing and spatial analyses by non-specialists. We also developed new tools for tissue de-arraying, image normalisation and cell segmentation to increase usability and reduce analysis subjectivity. We have also introduce new spatial analysis tools for the partition of tissue architectures and cellular microenvironments. We demonstrate the capabilities of CellMAPS in various diseases captured using different multiplex imaging platforms. Overall, CellMAPS provides a platform for inexperienced laboratories to implement multiplex imaging and complex spatial analyses, which ultimately should lead to the broader adoption of these technologies in the biomedical field.

bioinformatics↗

bioRxiv2022

Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis

COVID-19 placentitis, a rare complication of maternal SARS-CoV-2 infection, only shows detectable virus in the placenta of a subset of cases. We provide a deep multi-omic spatial characterisation of placentitis from obstetrically complicated maternal COVID-19 infection. We found that SARS-CoV-2 infected placentas have a distinct transcriptional and immunopathological signature. This signature overlaps with virus-negative cases supporting a common viral aetiology. An inverse correlation between viral load and disease duration suggests viral clearance over time. Quantitative spatial analyses revealed a unique microenvironment surrounding virus-infected trophoblasts characterised by PDL1-expressing macrophages, T-cell exclusion, and interferon blunting. In contrast to uninfected mothers, ACE2 was localised to the maternal side of the placental trophoblast layer of almost all mothers with placental SARS-CoV-2 infection, which may explain variable susceptibility to placental infection. Our results demonstrate a pivotal role for direct placental SARS-CoV-2 infection in driving the unique immunopathology of COVID-19 placentitis. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

immunology↗

bioRxiv2021

LRR protein RNH1 inhibits inflammasome activation through proteasome-mediated degradation of Caspase-1 and is associated with adverse clinical outcomes in COVID-19 patients.

Inflammasomes are cytosolic innate immune sensors of pathogen infection and cellular damage that induce caspase-1 mediated inflammation upon activation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and can be detrimental, such as in COVID-19. However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine rich repeat (LRR) protein Ribonuclease inhibitor (RNH1), which shares homology with LRRs of NLRP proteins, attenuates inflammasome activation. Deletion of RNH1 in macrophages increases IL-1{beta} production and caspase-1 activation for inflammasome stimuli. Mechanistically, RNH1 decreases pro-IL-1{beta} expression and induces proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and LPS-induced endotoxemia, which are dependent on caspase-1, respectively show increased neutrophil infiltration and lethality in Rnh1-/- mice compared to WT mice. Furthermore, RNH1 protein levels are negatively correlated with inflammation and disease severity in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity.

immunology↗

bioRxiv2020

High-Dimensional mass cytometry analysis reveals systemic immune perturbations in paediatric cancer influenced by age

Systemic immunity plays an important role in cancer immune surveillance and therapy but there is little detailed knowledge about the immune status of healthy children or children with cancer. We performed a high dimensional single cell analysis of systemic immunity in pediatric cancer patients and age-matched healthy children. In young children with cancer (age < 8years) NK cells were decreased in frequency, maturity, expression of perforin and granzyme-B, and were less cytotoxic in ex vivo assays. NK cell activity was restored after in vitro culture with interleukin-2. In contrast, older children with cancer (>8 years old) had decreased naive CD4 and CD8 T-cells with concomitant increases in effector memory and T effector memory RA-revertant (TEMRA) T-cells. These immunological changes in pediatric cancer patients are relevant to the better understanding of how cancers diagnosed in childhood interact with systemic immunity and could inform the development and application of effective immune-modulating therapies in the pediatric population. One Sentence SummaryHigh dimensional analysis of systemic immunity in pediatric cancer patients reveals clinically relevant immune changes in NK and T-cells that vary with patient age.

immunology↗