Vascular endothelial growth factor A is known to play a central role in tumor angiogenesis. Several studies showed that VEGF-A is also an immunosuppressive factor. In tumor-bearing hosts, VEGF-A can ...modulate immune cells (DC, MDSC, TAM) to induce the accumulation of regulatory T-cells while simultaneously inhibiting T-cell functions. Furthermore, VEGFR-2 expression on activated T-cells and FoxP3
regulatory T-cells also allow a direct effect of VEGF-A. Anti-angiogenic agents targeting VEGF-A/VEGFR contribute to limit tumor-induced immunosuppression. Based on interesting preclinical studies, many clinical trials have been conducted to investigate the efficacy of anti-VEGF-A/VEGFR treatments combined with immune checkpoint blockade leading to the approvement of these associations in different tumor locations. In this review, we focus on the impact of VEGF-A on immune cells especially regulatory and effector T-cells and different therapeutic strategies to restore an antitumor immunity.
Although there is no doubt from an empirical viewpoint that reflex mechanisms can contribute to tongue motor control in humans, there is limited neurophysiological evidence to support this idea. ...Previous results failing to observe any tonic stretch reflex in the tongue had reduced the likelihood of a reflex contribution in tongue motor control. The current study presents experimental evidence of a human tongue reflex in response to a sudden stretch while holding a posture for speech. The latency was relatively long (50 ms), which is possibly mediated through cortical-arc. The activation peak in a speech task was greater than in a non-speech task while background activation levels were similar in both tasks, and the peak amplitude in a speech task was not modulated by the additional task to react voluntarily to the perturbation. Computer simulations with a simplified linear mass-spring-damper model showed that the recorded muscle activation response is suited for the generation of tongue movement responses that were observed in a previous study with the appropriate timing when taking into account a possible physiological delay between reflex muscle activation and the corresponding force. Our results evidenced clearly that reflex mechanisms contribute to tongue posture stabilization for speech production.
We present a novel functional magnetic resonance imaging paradigm for second-person neuroscience. The paradigm compares a human social interaction (human-human interaction, HHI) to an interaction ...with a conversational robot (human-robot interaction, HRI). The social interaction consists of 1 min blocks of live bidirectional discussion between the scanned participant and the human or robot agent. A final sample of 21 participants is included in the corpus comprising physiological (blood oxygen level-dependent, respiration and peripheral blood flow) and behavioural (recorded speech from all interlocutors, eye tracking from the scanned participant, face recording of the human and robot agents) data. Here, we present the first analysis of this corpus, contrasting neural activity between HHI and HRI. We hypothesized that independently of differences in behaviour between interactions with the human and robot agent, neural markers of mentalizing (temporoparietal junction (TPJ) and medial prefrontal cortex) and social motivation (hypothalamus and amygdala) would only be active in HHI. Results confirmed significantly increased response associated with HHI in the TPJ, hypothalamus and amygdala, but not in the medial prefrontal cortex. Future analysis of this corpus will include fine-grained characterization of verbal and non-verbal behaviours recorded during the interaction to investigate their neural correlates. This article is part of the theme issue 'From social brains to social robots: applying neurocognitive insights to human-robot interaction'.
A quick correction mechanism of the tongue has been formerly experimentally observed in speech posture stabilization in response to a sudden tongue stretch perturbation. Given its relatively short ...latency (< 150 ms), the response could be driven by somatosensory feedback alone. The current study assessed this hypothesis by examining whether this response is induced in the absence of auditory feedback. We compared the response under two auditory conditions: with normal versus masked auditory feedback. Eleven participants were tested. They were asked to whisper the vowel /e/ for a few seconds. The tongue was stretched horizontally with step patterns of force (1 N during 1 s) using a robotic device. The articulatory positions were recorded using electromagnetic articulography simultaneously with the produced sound. The tongue perturbation was randomly and unpredictably applied in one-fifth of trials. The two auditory conditions were tested in random order. A quick compensatory response was induced in a similar way to the previous study. We found that the amplitudes of the compensatory responses were not significantly different between the two auditory conditions, either for the tongue displacement or for the produced sounds. These results suggest that the observed quick correction mechanism is primarily based on somatosensory feedback. This correction mechanism could be learned in such a way as to maintain the auditory goal on the sole basis of somatosensory feedback.A quick correction mechanism of the tongue has been formerly experimentally observed in speech posture stabilization in response to a sudden tongue stretch perturbation. Given its relatively short latency (< 150 ms), the response could be driven by somatosensory feedback alone. The current study assessed this hypothesis by examining whether this response is induced in the absence of auditory feedback. We compared the response under two auditory conditions: with normal versus masked auditory feedback. Eleven participants were tested. They were asked to whisper the vowel /e/ for a few seconds. The tongue was stretched horizontally with step patterns of force (1 N during 1 s) using a robotic device. The articulatory positions were recorded using electromagnetic articulography simultaneously with the produced sound. The tongue perturbation was randomly and unpredictably applied in one-fifth of trials. The two auditory conditions were tested in random order. A quick compensatory response was induced in a similar way to the previous study. We found that the amplitudes of the compensatory responses were not significantly different between the two auditory conditions, either for the tongue displacement or for the produced sounds. These results suggest that the observed quick correction mechanism is primarily based on somatosensory feedback. This correction mechanism could be learned in such a way as to maintain the auditory goal on the sole basis of somatosensory feedback.
Elucidating mechanisms involved in tumor-induced immunosuppression is of great interest since it could help to improve cancer immunotherapy efficacy. Here we show that Hepatocyte Growth Factor (HGF), ...a pro-tumoral and proangiogenic factor, and its receptor c-Met are involved in regulatory T cells (Treg) accumulation in the peripheral blood of gastric cancer (GC) patients. We observed that c-Met is expressed on circulating monocytes from GC patients. The elevated expression on monocytes is associated with clinical parameters linked to an aggressive disease phenotype and correlates with a worse prognosis. Monocyte-derived dendritic cells from GC patients differentiated in the presence of HGF adopt a regulatory phenotype with a lower expression of co-stimulatory molecules, impaired maturation capacities, and an increased ability to produce interleukin-10 and to induce Treg differentiation in vitro. In the MEGA-ACCORD20-PRODIGE17 trial, GC patients received an anti-HGF antibody treatment (rilotumumab), which had been described to have an anti-angiogenic activity by decreasing proliferation of endothelial cells and tube formation. Rilotumumab decreased circulating Treg in GC patients. Thus, we identified that HGF indirectly triggers Treg accumulation via c-Met-expressing monocytes in the peripheral blood of GC patients. Our study provides arguments for potential alternative use of HGF/c-Met targeted therapies based on their immunomodulatory properties which could lead to the development of new therapeutic associations in cancer patients, for example with immune checkpoint inhibitors.
We present a novel functional magnetic resonance imaging paradigm for second-person neuroscience. The paradigm compares a human social interaction (human–human interaction, HHI) to an interaction ...with a conversational robot (human–robot interaction, HRI). The social interaction consists of 1 min blocks of live bidirectional discussion between the scanned participant and the human or robot agent. A final sample of 21 participants is included in the corpus comprising physiological (blood oxygen leveldependent, respiration and peripheral blood flow) and behavioural (recorded speech from all interlocutors, eye tracking from the scanned participant, face recording of the human and robot agents) data. Here, we present the first analysis of this corpus, contrasting neural activity between HHI and HRI. We hypothesized that independently of differences in behaviour between interactions with the human and robot agent, neural markers of mentalizing (temporoparietal junction (TPJ) and medial prefrontal cortex) and social motivation (hypothalamus and amygdala) would only be active in HHI. Results confirmed significantly increased response associated with HHI in the TPJ, hypothalamus and amygdala, but not in the medial prefrontal cortex. Future analysis of this corpus will include fine-grained characterization of verbal and non-verbal behaviours recorded during the interaction to investigate their neural correlates.
This article is part of the theme issue 'From social brains to social robots: applying neurocognitive insights to human–robot interaction'.
IntroductionWhen considering health-related impacts of foods, nutrient profile and (ultra)processing are two complementary dimensions. The Nutri-Score informs on the nutrient profile dimension. ...Recently, mounting evidence linked ultraprocessed food consumption to various adverse health outcomes, independently of their nutrient profile. To inform consumers about each of these health-related dimensions of food, we tested, in a randomised controlled trial, if a graphically modified version ‘Nutri-Score V.2.0’, including a black ‘ultraprocessed’ banner, would improve the capacity of consumers to rank products according to their nutrient profile and to detect those ultra-processed, compared with a no-label situation.Methods21 159 participants included in the NutriNet-Santé web-cohort were randomly assigned to a control arm (no front-of-pack label) or an experimental arm (Nutri-Score 2.0) and were presented an online questionnaire with three sets of food products (cookies, breakfast cereals and ready-to-eat meals) to rank according to nutrient profile and to identify ultraprocessed foods. The primary outcome was objective understanding of nutrient profile and ultraprocessing, represented by a score of correct answers. Secondary outcomes were purchasing intentions and the healthiest-perceived product. Multinomial logistic regressions were performed.ResultsThe Nutri-Score V.2.0 increased the objective understanding of both the nutrient profile dimension (OR highest vs lowest score category=29.0 (23.4–35.9), p<0.001) and the ultraprocessing dimension (OR=174.3 (151.4–200.5), p<0.001). Trends were similar for cookies, breakfast cereals and ready-to-eat meals. The Nutri-Score V.2.0 had a positive effect on purchasing intentions and on the products perceived as the healthiest.ConclusionThis randomised controlled trial demonstrates the interest of a front-of-pack label combining the Nutri-Score (informing on the nutrient profile dimension) with an additional graphic mention, indicating when the food is ultraprocessed, compared with a no-label situation. Our results show that a combined label enabled participants to independently understand these two complementary dimensions of foods.Trial registration numberNCT05610930.
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