Hodgkin/Reed-Sternberg cells induce GPNMB expression and release from macrophages to suppress T-cell responses to the Epstein-Barr virus-encoded LMP2A protein.

Not available.

Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma.

In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2-fold enrichment in programmed cell death-1 (PD-1) and T-cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra-tumoral protein expression of PD-1+ (and/or TIGIT+) CD4+ T-cells and PD-1+CD8+ T-cells in NLPHL compared to cHL. This included T-cells that rosetted with lymphocyte predominant (LP) and Hodgkin Reed-Sternberg (HRS) cells. In NLPHL, intra-tumoral PD-1+CD4+ T-cells frequently expressed TCF-1, a marker of heightened T-cell response to ICB. The peripheral blood signatures between HLs were also distinct, with higher levels of PD-1+TIGIT+ in TH1, TH2, and regulatory CD4+ T-cells in NLPHL versus cHL. Circulating PD-1+CD4+ had high levels of TCF-1. Notably, in both lymphomas, highly expanded populations of clonal TIGIT+PD-1+CD4+ and TIGIT+PD-1+CD8+ T-cells in the blood were also present in the TME, indicating that immune-checkpoint expressing T-cells circulated between intra-tumoral and blood compartments. In in vitro assays, ICB was capable of reducing rosette formation around LP and HRS cells, suggesting that disruption of rosetting may be a mechanism of action of ICB in HL. Overall, results indicate that further evaluation of ICB is warranted in NLPHL.

Determination of microbial numbers in anaerobically digested biofertilisers.

This study aimed to quantity total numbers of bacteria, fungi and archaea in different types of commercial liquid anaerobic digestates, and to identify common patterns in their microbial numbers post-digestion and possible implications of their use as biofertiliser. Relationships between microbial numbers and physical-chemical traits of the digestates were also investigated. Quantification was performed using culturable and molecular (quantitative PCR) approaches. Bacterial and fungal CFUs ranged up to five orders of magnitude (105-1010; 0-105 g-1 DW, respectively) between different types of anaerobic digestates. Bacterial, archaeal and fungal gene copy numbers (GCN) varied by two orders of magnitude (108-1010; 107-109; 104-106 g-1 DW, respectively) between digestates. All microbial variables analysed showed significant differences between the different types of anaerobic digestate investigated (p < 0.05). Culturable microbial numbers for fungi (6.43 × 104 CFU g-1 DW) were much lower than for bacteria (2.23 × 109 CFU g-1 DW). Gene copy numbers were highest for bacteria (16S) (1.09 × 1010 g-1 DW), followed by archaea (16S) (5.87 × 108 g-1 DW), and fungi (18S) (1.77 × 106 g-1 DW). Liquid anaerobic digestates were predominantly dominated by bacteria, followed by archaeal and fungal populations. At 50% similarity level, the microbial profiles of the eleven anaerobic digestates tested separated into just two groups, indicating a broad relative degree of similarity in terms of microbial numbers. Higher bacterial (16S) GCN was associated with low OM and C/N ratio in digestates.

Physical-chemical traits, phytotoxicity and pathogen detection in liquid anaerobic digestates.

Anaerobic digestates, which are co-products from biogas production, have been recognised as potential biofertilisers for their benefits in nutrient recovery and recycling of different types of organic wastes. Due to the increasing number of different types of organic wastes being used to produce biogas, it is necessary to identify how different types of anaerobic digestates vary in their physical-chemical traits, and how these can impact upon their use as fertilisers. In addition, safe land spreading of anaerobic digestates must be within recommended limits for potentially toxic elements (PTEs) and pathogens. This study analysed physical-chemical traits, phytotoxicity, PTEs and indicator pathogens in a set of eleven different commercial liquid anaerobic digestates from Ireland and the UK, and compared them to the Irish draft standard for digestate. Liquid anaerobic digestates exhibited significant differences (P < 0.001) for most of the physical and chemical traits evaluated, with higher variability found for dry matter (DM) and K (CV = 17.2 and 16.8 respectively), and lower variation for pH and P (CV = 1.78 and 3.55 respectively). PTE concentrations were in general within recommended limits; nevertheless, some digestates showed higher concentrations than the recommended limits for Pb, Zn and Cu. Digestate from wastewater treatment feedstock was shown to be high in PTEs. Anaerobic digestates were found to negatively affect early stages of seed germination, but phytotoxicity effects were decreased by dilution in water. Levels of Salmonella spp. and E. coli were within recommended limits for most of the anaerobic digestates analysed.