Tumor associated macrophages (TAMs) are important components of the tumor microenvironment (TME). They are characterized by a remarkable functional plasticity, thereby mostly promoting cancer progression. Changes in immune cell metabolism are paramount for this functional adaptation. Here, we review the functional consequences of the metabolic programming of TAMs and the influence of local and systemic targeted therapies on the metabolic characteristics of the TME that shape the functional phenotype of the TAMs. Understanding these metabolic changes within the context of the cross-talk between the different components of the TME including the TAMs and the tumor cells is an essential step that can pave the way towards identifications of ways to improve responses to different treatments, to overcome resistance to treatments, tumor progression and reduce treatment-specific toxicity.
Alcohol intoxication is known to affect many aspects of human behavior and cognition; one of such affected systems is articulation during speech production. Although much research has revealed that alcohol negatively impacts pronunciation in a first language (L1), there is only initial evidence suggesting a potential beneficial effect of inebriation on articulation in a non-native language (L2). The aim of this study was thus to compare the effect of alcohol consumption on pronunciation in an L1 and an L2. Participants who had ingested different amounts of alcohol provided speech samples in their L1 (Dutch) and L2 (English), and native speakers of each language subsequently rated the pronunciation of these samples on their intelligibility (for the L1) and accent nativelikeness (for the L2). These data were analyzed with generalized additive mixed modeling. Participants’ blood alcohol concentration indeed negatively affected pronunciation in L1, but it produced no significant effect on the L2 accent ratings. The expected negative impact of alcohol on L1 articulation can be explained by reduction in fine motor control. We present two hypotheses to account for the absence of any effects of intoxication on L2 pronunciation: (1) there may be a reduction in L1 interference on L2 speech due to decreased motor control or (2) alcohol may produce a differential effect on each of the two linguistic subsystems.
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