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Cancer stem cells (CSCs) are known for their superior tumor-initiating and tumor-repopulating potential, partly reflecting their pronounced ability to evade immune recognition. Liu and colleagues recently identified a new aldehyde dehydrogenase (ALDH)-dependent mechanism whereby triple-negative breast CSCs evade immunosurveillance upon recruitment of myeloid-derived suppressor cells. [ABSTRACT FROM AUTHOR]

Two recent reports in Nature highlight a novel mechanism of immunoevasion that relies on the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-dependent epigenetic suppression of endogenous retroelements in melanoma cells. Because SETDB1 is highly expressed by the stem cell compartment, these findings delineate an innovative strategy for restoring cancer stem cell immunosurveillance. [ABSTRACT FROM AUTHOR]

Two recent reports in Nature highlight a novel mechanism of immunoevasion that relies on the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-dependent epigenetic suppression of endogenous retroelements in melanoma cells. Because SETDB1 is highly expressed by the stem cell compartment, these findings delineate an innovative strategy for restoring cancer stem cell immunosurveillance. [ABSTRACT FROM AUTHOR]

In most (if not all) solid tumors, malignant cells are outnumbered by their non-malignant counterparts, including immune, endothelial and stromal cells. However, while the mechanisms whereby cancer cells adapt to microenvironmental perturbations have been studied in great detail, relatively little is known on stress responses in non-malignant compartments of the tumor microenvironment. Here, we discuss the mechanisms whereby cancer-associated fibroblasts and other cellular components of the tumor stroma react to stress in the context of an intimate crosstalk with malignant, endothelial and immune cells, and how such crosstalk influences disease progression and response to treatment. [ABSTRACT FROM AUTHOR]

Abstract Introduction Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter <2.5 μm (PM 2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM 2.5 and PM 10 and gastric and UADT cancer incidence in European adults. Methods Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. Results Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m3 of PM 2.5 _S was 1.92 (95%-confidence interval (95%-CI) 1.13;3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I2 = 0%), and 1.63 (95%-CI 0.88;3.01) for PM 2.5 _Zn (I2 = 70%). For the other elements in PM 2.5 and all elements in PM 10 including PM 10 _S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM 2.5 _S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM 2.5 decreased whereas that for PM 2.5 _S was robust. Conclusion This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM 2.5 _S but not PM 10 _S, suggesting that S in PM 2.5 or correlated air pollutants may contribute to the risk of gastric cancer. Highlights • Population-based cohorts from 6 European countries (227,044 participants) • Copper, iron, zinc, sulphur, nickel, vanadium, silicon and potassium in PM 2.5 and PM 10 were studied. • Statistically significant strong association of gastric cancer with sulphur in PM 2.5 , but not in PM 10 • No association of gastric cancer with any of the other 7 elements tested • No association with upper aerodigestive tract cancer [ABSTRACT FROM AUTHOR]

Abstract Background Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and cardiovascular diseases, suggesting the involvement of common altered molecular pathways. Objectives The goal was to find intermediate metabolites or metabolic pathways that could be associated with both air pollutants and health outcomes (“meeting-in-the-middle”), thus shedding light on mechanisms and reinforcing causality. Methods We applied a statistical approach named ‘meet-in-the-middle’ to untargeted metabolomics in two independent case-control studies nested in cohorts on adult-onset asthma (AOA) and cardio-cerebrovascular diseases (CCVD). We compared the results to identify both common and disease-specific altered metabolic pathways. Results A novel finding was a strong association of AOA with ultrafine particles (UFP; odds ratio 1.80 [1.26, 2.55] per increase by 5000 particles/cm3). Further, we have identified several metabolic pathways that potentially mediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolism pathway was associated with air pollution exposure, AOA and CCVD. Conclusions Our results suggest common pathway perturbations may occur as a consequence of chronic exposure to air pollution leading to increased risk for both AOA and CCVD. Highlights • Strong association of long-term ultrafine particle exposure with adult-onset asthma • Linoleate metabolism and carnitine shuttle as “meeting-in-the-middle” pathways. • Metabolic pathways mediate the air pollution effects on health outcomes. [ABSTRACT FROM AUTHOR]

An increasing number of epidemiological studies suggest that adverse health effects of air pollution may be related to particulate matter (PM) composition, particularly trace metals. However, we lack comprehensive data on the spatial distribution of these elements. We measured PM 2.5 and PM 10 in twenty study areas across Europe in three seasonal two-week periods over a year using Harvard impactors and standardized protocols. In each area, we selected street (ST), urban (UB) and regional background (RB) sites (totaling 20) to characterize local spatial variability. Elemental composition was determined by energy-dispersive X-ray fluorescence analysis of all PM 2.5 and PM 10 filters. We selected a priori eight (Cu, Fe, K, Ni, S, Si, V, Zn) well-detected elements of health interest, which also roughly represented different sources including traffic, industry, ports, and wood burning. PM elemental composition varied greatly across Europe, indicating different regional influences. Average street to urban background ratios ranged from 0.90 (V) to 1.60 (Cu) for PM 2.5 and from 0.93 (V) to 2.28 (Cu) for PM 10 . Our selected PM elements were variably correlated with the main pollutants (PM 2.5 , PM 10 , PM 2.5 absorbance, NO 2 and NO x ) across Europe: in general, Cu and Fe in all size fractions were highly correlated (Pearson correlations above 0.75); Si and Zn in the coarse fractions were modestly correlated (between 0.5 and 0.75); and the remaining elements in the various size fractions had lower correlations (around 0.5 or below). This variability in correlation demonstrated the distinctly different spatial distributions of most of the elements. Variability of PM 10 _Cu and Fe was mostly due to within-study area differences (67% and 64% of overall variance, respectively) versus between-study area and exceeded that of most other traffic-related pollutants, including NO 2 and soot, signaling the importance of non-tailpipe (e.g., brake wear) emissions in PM. [ABSTRACT FROM AUTHOR]

Abstract: The ESCAPE study (European Study of Cohorts for Air Pollution Effects) investigates long-term effects of exposure to air pollution on human health in Europe. This paper documents the spatial variation of measured NO2 and NO x concentrations between and within 36 ESCAPE study areas across Europe. In all study areas NO2 and NO x were measured using standardized methods between October 2008 and April 2011. On average, 41 sites were selected per study area, including regional and urban background as well as street sites. The measurements were conducted in three different seasons, using Ogawa badges. Average concentrations for each site were calculated after adjustment for temporal variation using data obtained from a routine monitor background site. Substantial spatial variability was found in NO2 and NO x concentrations between and within study areas; 40% of the overall NO2 variance was attributable to the variability between study areas and 60% to variability within study areas. The corresponding values for NO x were 30% and 70%. The within-area spatial variability was mostly determined by differences between street and urban background concentrations. The street/urban background concentration ratio for NO2 varied between 1.09 and 3.16 across areas. The highest median concentrations were observed in Southern Europe, the lowest in Northern Europe. In conclusion, we found significant contrasts in annual average NO2 and NO x concentrations between and especially within 36 study areas across Europe. Epidemiological long-term studies should therefore consider different approaches for better characterization of the intra-urban contrasts, either by increasing of the number of monitors or by modelling. [Copyright &y& Elsevier]

Abstract: The ESCAPE study (European Study of Cohorts for Air Pollution Effects) investigates relationships between long-term exposure to outdoor air pollution and health using cohort studies across Europe. This paper analyses the spatial variation of PM2.5, PM2.5 absorbance, PM10 and PMcoarse concentrations between and within 20 study areas across Europe. We measured NO2, NO x , PM2.5, PM2.5 absorbance and PM10 between October 2008 and April 2011 using standardized methods. PMcoarse was determined as the difference between PM10 and PM2.5. In each of the twenty study areas, we selected twenty PM monitoring sites to represent the variability in important air quality predictors, including population density, traffic intensity and altitude. Each site was monitored over three 14-day periods spread over a year, using Harvard impactors. Results for each site were averaged after correcting for temporal variation using data obtained from a reference site, which was operated year-round. Substantial concentration differences were observed between and within study areas. Concentrations for all components were higher in Southern Europe than in Western and Northern Europe, but the pattern differed per component with the highest average PM2.5 concentrations found in Turin and the highest PMcoarse in Heraklion. Street/urban background concentration ratios for PMcoarse (mean ratio 1.42) were as large as for PM2.5 absorbance (mean ratio 1.38) and higher than those for PM2.5 (1.14) and PM10 (1.23), documenting the importance of non-tailpipe emissions. Correlations between components varied between areas, but were generally high between NO2 and PM2.5 absorbance (average R 2 = 0.80). Correlations between PM2.5 and PMcoarse were lower (average R 2 = 0.39). Despite high correlations, concentration ratios between components varied, e.g. the NO2/PM2.5 ratio varied between 0.67 and 3.06. In conclusion, substantial variability was found in spatial patterns of PM2.5, PM2.5 absorbance, PM10 and PMcoarse. The highly standardized measurement of particle concentrations across Europe will contribute to a consistent assessment of health effects across Europe. [Copyright &y& Elsevier]