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The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8 + TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226 hi TILs were highly functional. This correlation was seen also in TILs isolated from HNSCC patients. Mutation of CD226 at tyrosine 319 (Y319) led to increased CD226 surface expression, enhanced anti-tumor immunity and improved efficacy of immune checkpoint blockade (ICB). Mechanistically, tumor-derived CD155, the ligand for CD226, initiated phosphorylation of Y319 by Src kinases, thereby enabling ubiquitination of CD226 by CBL-B, internalization, and proteasomal degradation. In pre-treatment samples from melanoma patients, CD226 + CD8 + T cells correlated with improved progression-free survival following ICB. Our findings argue for the development of therapies aimed at maintaining the expression of CD226., Competing Interests: Declaration of Interests M.J.S. has research agreements with Bristol Myers Squibb (BMS) and Tizona Therapeutics and is on the Scientific Advisory Board of Tizona Therapeutics and Compass Therapeutics. T.B. has research agreements with BMS. B.G.M.H. is a consultant advisor to BMS, Merck Sharp and Dohme, Roche, AstraZenca, Pfizer, Eisai, and Takeda and has research agreements with Amgen. G.V.L. is a consultant advisor to Aduro, Amgen, Mass-Array, BMS, Merck MSD, Novartis, Roche, OncoSec Medical, Sandoz, and Pierre Fabre. A.M. is a consultant advisor for BMS, Merck MSD, Novartis, Roche, and Pierre Fabre. W.C.D. declares a scientific research agreement with BMS, consulting agreements with Omeros Corp. and Cascadia Drug Development Group, and receipt of speaker’s honoraria from Amgen. A.V. has research agreements with BMS. R.A.S. has received fees for professional services from Novartis Pharma AG, MSD Sharp & Dohme (Australia), NeraCare, AMGEN Inc., BMS, Novartis Pharmaceuticals Australia Pty. Limited, Myriad Genetics GmbH, GlaxoSmithKline Australia. L.F. reported grants from the Swiss National Science Foundation, Swiss Cancer League, Hookipa Pharma, Krebsliga Schweiz, and Novartis Foundation as well as an advisory role for Novartis and BMS. S.E.N. has a research agreement with Servier. M.B., M.J.S., and T.B. have registered a patent for the use of CD226 in cancer immunotherapies (Australian Provisional Patent Application No. 2019900621)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Both earthworms and terrestrial isopods have been used to evaluate the quality of contaminated soil by NPs. However, most experiments have been conducted in the laboratory and under greenhouse conditions. Besides, little is known of Fe accumulation in earthworms from iron NPs (Fe NPs) under natural conditions. Therefore, the objective of this research was to evaluate the effect of manufactured NPs on the accumulation of Fe in macroinvertebrates from forest soil. Our results revealed that earthworms consume low amounts of Fe in a concentration of 1000 mg Fe NPs kg -1 of dry soil, with a behavior constant over time. Besides, we observed that earthworms could not detect Fe at low concentrations (1 or 10 mg Fe NPs kg -1 ), so they do not limit soil consumption, which translates into high amounts of Fe in their bodies. By contrast, the content of Fe in organisms is inversely proportional to increasing concentrations in the soil (R 2 = -0.41, p < 0.05). Therefore, although studies are needed, in addition to considering environmental factors and the physicochemical properties of the soil, endogenous worms in the evaluated area could, under natural conditions, be useful to inform us of contamination of NP manufactured from Faith. Besides, for future research, a novel methodology should be considered to demonstrate more realistic avoidance behavior under field conditions., (© 2020 The Authors.)

Wastewater treatment plants face major social concern towards removal of problematic pollutants such as fat oils and grease (FOG). In this context, the main objective of the present work was to select natural bacterial isolates from different polluted sites and evaluate them comparatively to isolates from commercial products, for improved bioremediation strategies and bioaugmentation. In total, 196 isolates were analysed for genomic diversity by two PCR-fingerprinting methods and screened for biodegradation potential with pollutants as sole carbon source. The net area under curve (NAUC) was used for preliminary evaluation of growth ability in M9 medium supplemented with oleic acid and triolein. A principal component analysis of all NAUC data showed that natural isolates presented higher overall biodegradation ability and enabled the selection of 11 natural isolates for lipid degradation assays. Selected isolates were identified by 16S rRNA gene sequencing as members of genera with previously described degradative strains, namely, Acinetobacter (1), Aeromonas (2), Bacillus (1), Pseudomonas (1) and Staphylococcus (6). Best biodegradation results in 7-days assay of FOG content removal were 37.9% for oleic acid and 19.1% for triolein by an Aeromonas sp. isolate and a Staphylococcus cohnii isolate, respectively. A respirometry approach confirmed their higher oxygen uptake rates, although longer adaptation phases where required by the Aeromonas sp. isolate. Consequently, these isolates showed great potential for future bioaugmentation products, to promote FOG degradation, for both in situ and ex situ approaches.