Natural Killer T-Cell Agonist alpha-Galactosylceramide and PD-1 Blockade Synergize to Reduce Tumor Development in a Preclinical Model of Colon Cancer
FRONTIERS IN IMMUNOLOGY
Authors: Wang, Ying; Bhave, Madhura S.; Yagita, Hideo; Cardell, Susanna L.
Abstract
Murine and human invariant natural killer T (iNKT) lymphocytes are activated by alpha-galactosylceramide (alpha-GalCer) presented on CD1d. alpha-GalCer was first described as a lipid that had strong anti-metastatic effects in a mouse melanoma model, and it has subsequently been shown to induce efficient iNKT cell dependent tumor immunity in several tumor models. We have shown that alpha-GalCer treatment leads to a weak reduction of polyp burden in the autochthonous Apc(Min/+) mouse model for human colon cancer, however this treatment resulted in upregulation of the inhibitory receptor PD-1 on iNKT cells. While anti-PD-1 treatment can prevent immune-suppression in other cancer types, human colon cancer is generally resistant to this treatment. Here we have used the Apc(Min/+) model to investigate whether a combined treatment with alpha-GalCer and PD-1 blockade results in improved effects on polyp development. We find that PD-1 expression was high on T cells in polyps and lamina propria (LP) of Apc(Min/+) mice compared to polyp free (Apc+/+) littermates. Anti-PD-1 treatment alone promoted Tbet expression in iNKT cells and CD4 T cells, but did not significantly reduce polyp numbers. However, the combined treatment with anti-PD-1 and alpha-GalCer had synergistic effects, resulting in highly significant reduction of polyp numbers in the small and large intestine. Addition of PD-1 blockade to alpha-GalCer treatment prevented loss of iNKT cells that were skewed towards a TH1-like iNKT1 phenotype specifically in polyps. It also resulted in TH1 skewing and increased granzyme B expression of CD4 T cells. Taken together this demonstrates that a combination of immune stimulation targeting iNKT cells and checkpoint blockade may be a promising approach to develop for improved tumor immunotherapy.
Assessing the ancillary service potential of electric vehicles to support renewable energy integration in touristic islands: A case study from Balearic island of Menorca
RENEWABLE ENERGY
Authors: Raveendran, Visal; Alvarez-Bel, Carlos; Nair, Manjula G.
Abstract
The potential of e-mobility to participate in intermittency flattening ancillary services (AS) to support solar photo-voltaic (PV) grid integration is analysed in this paper. First, the capability of Plug-in Electric Vehicles (PEVs) to act as Energy Storage Systems (ESS) based on daily energy storage potential (ESP) with and without vehicle-to-grid (V2G) services is studied. Mobility behaviour and penetration levels of various categories of vehicles-cars, vans, trucks, buses and motorcycles in the island are modeled using traffic data from Menorca island. Next, ancillary service (AS) potential of 1000 PEVs to support solar PV grid integration is analysed. A crucial parameter of PEVs to offer uni-V2G services under aggregator to participate in hour-ahead AS market, termed achievable power capacity (APC), is explored. Results showed that, for bidirectional V2G services in summer, ESP can reach up to 100 MWh for minimum (P1) and 375 MWh for maximum (P6) penetration levels considered. The regulation potential for every 1000 private PEVs aggregated to a maximum of 4.6 MW and reserve potential to a maximum of 5.25 MW under coordinated charging. This reveals the great potential of PEVs in offering AS in small touristic islands. (C) 2020 Elsevier Ltd. All rights reserved.