Tongue reflex for speech posture control.

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.

Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients.

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.

Direct and Indirect Modulation of T Cells by VEGF-A Counteracted by Anti-Angiogenic Treatment.

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 FoxP3high 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.

Brain activity during reciprocal social interaction investigated using conversational robots as control condition.

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'.