Stormwater treatment technologies to manage runoff during rain events are primarily designed to reduce flood risks, settle suspended solids and concurrently immobilise metals and nutrients. Life ...Cycle Assessment (LCA) is scarcely documented for stormwater systems despite their ubiquitous implementation. LCA modelling quantified the environmental impacts associated with the materials, construction, transport, operation and maintenance of different stormwater treatment systems. A pre-fabricated concrete vortex unit, a sub-surface sandfilter and a raingarden, all sized to treat a functional unit of 35 m3 of stormwater runoff per event, were evaluated. Eighteen environmental mid-point metrics and three end-point ‘damage assessment’ metrics were quantified for each system's lifecycle. Climate change (kg CO2 eq.) dominated net environmental impacts, with smaller contributions from human toxicity (kg 1,4-DB eq.), particulate matter formation (kg PM10 eq.) and fossil depletion (kg oil eq.). The concrete unit had the highest environmental impact of which 45% was attributed to its maintenance while impacts from the sandfilters and raingardens were dominated by their bulky materials (57%) and transport (57%), respectively. On-site infiltrative raingardens, a component of green infrastructure (GI), had the lowest environmental impacts because they incurred lower maintenance and did not have any concrete which is high in embodied CO2. Smaller sized raingardens affording the same level of stormwater treatment had the lowest overall impacts reinforcing the principle that using fewer resources reduces environmental impacts. LCA modelling can serve as a guiding tool for practitioners making environmentally sustainable solutions for stormwater treatment.
•LCA environmental impacts of stormwater treatment systems were determined.•Concrete-based treatment unit had highest environmental impacts.•Sandfilters and raingardens impacts were dominated by materials and transport.•Infiltrative raingardens had lowest environmental impacts.
Aim
Visceral obesity is a key risk factor in the development of oesophagogastric junctional adenocarcinoma (OGJ), predominantly via generation of systemic low grade inflammation. Obesity-induced ...inflammation promotes resistance to current standards of care, enhancing tumour cell growth and survival. This study investigates the effect of the visceral adipose tissue secretome from OGJ patients with early versus advanced tumours on T-cell immunity and the role of immune checkpoint blockade in enhancing anti-tumour immunity.
Methods and results
Visceral adipose conditioned media (ACM) from both early and late-stage OGJ patients significantly altered T cell activation status, upregulating co-stimulatory marker CD27 on T cells. ACM from both early and late-stage OGJ patients significantly altered immune checkpoint expression profiles downregulating immune checkpoints (ICs) on the surface of dual Th1/17-like and Th17-like cells and upregulating ICs on the surface of Th1-like cells and Treg cells. ACM derived from early-stage OGJ patients but not late-stage OGJ patients increased IFN-γ production by T cells. The addition of immune checkpoint blockers (ICBs) did not increase IFN-γ production by T cells in the presence of late-stage ACM, collectively highlighting the dichotomous immunostimulatory effect of early-stage ACM and immune-inhibitory effect of late-stage ACM. Interestingly, ACM from early-stage OGJ patients was more pro-inflammatory than ACM from late-stage patients, reflected by decreased levels of IL-17A/F, TNF-α, IL-1RA and IL-5.
Conclusion
The ACM-induced upregulation of ICs on T cells highlights a therapeutic vulnerability that could be exploited by ICBs to harness anti-cancer immunity and improve clinical outcomes for OGJ patients.
Graphical Abstract
Schematic workflow – (A) visceral adipose tissue was taken from OAC patients at time of surgery and cultured for 72 h in media. (B) The harvested ACM was co-cultured with healthy donor PBMCs that were concurrently activated with anti-CD3/28 for 48 h and T cell immunophenotyping was carried out by flow cytometry. Key findings – (A) Early and late stage ACM enhanced a Th1-like phenotype and upregulated CTLA-4 on Th1-like cells. A Th17-like phenotype was also enhanced in addition with a Treg-like phenotype. CTLA-4 and PD-L1 were upregulated on the surface of Treg-like cells. (B) ICB-attenuated IL-17 production by T cells. However, ACM attenuated ICB-mediated reduction in IL-10 production by T cells. Higher levels of pro-inflammatory factors were found in early stage ACM compared with late stage ACM.
Combining immunostimulatory chemotherapies with immunotherapy is an attractive strategy to enhance treatment responses in oesophagogastric junctional adenocarcinoma (OGJ). This study investigates the ...immunostimulatory properties of FLOT, CROSS and MAGIC chemotherapy regimens in the context of OGJ using in vitro and ex vivo models of the treatment-naïve and post-chemotherapy treated tumour microenvironment. FLOT and CROSS chemotherapy regimens increased surrogate markers of immunogenic cell death (HMGB1 and HLA-DR), whereas the MAGIC treatment regimen decreased HMGB1 and HLA-DR on OGJ cells (markedly for epirubicin). Tumour-infiltrating and circulating T cells had significantly lower CD27 expression and significantly higher CD69 expression post-FLOT and post-CROSS treatment. Similarly
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the supernatant from FLOT- and CROSS-treated OGJ cell lines and from FLOT- and CROSS-treated OGJ biopsies cultured ex vivo also decreased CD27 and increased CD69 expression on T cells. Following 48 h treatment with post-FLOT and post-CROSS tumour conditioned media the frequency of CD69
+
T cells in culture negatively correlated with the levels of soluble immunosuppressive pro-angiogenic factors in the conditioned media from ex vivo explants. Supernatant from FLOT- and CROSS-treated OGJ cell lines also increased the cytotoxic potential of healthy donor T cells ex vivo and enhanced OGJ patient-derived lymphocyte mediated-killing of OE33 cells ex vivo
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Collectively, this data demonstrate that FLOT and CROSS chemotherapy regimens possess immunostimulatory properties, identifying these chemotherapy regimens as rational synergistic partners to test in combination with immunotherapy and determine if this combinatorial approach could boost anti-tumour immunity in OGJ patients and improve clinical outcomes.
