Mello, M. | bioRxiv Science

bioRxiv2024

Taking the perspective of an embodied avatar modulates the temporal dynamics of vicarious pain and pleasure: a combined Immersive Virtual Reality and EEG study

Observing negative and positive valence virtual stimuli can influence the onlookers subjective and brain reactivity. However, the relationship between vicarious pain and pleasure, observers perspective taking and cerebral activity remains underexplored. To address this gap, we asked 24 healthy participants to passively observe pleasant, painful, and neutral stimuli delivered to a virtual hand seen from a first-person (1PP) or third-person perspective (3PP) while undergoing time and time-frequency EEG recording. Participants reported a stronger sense of ownership over the virtual hand seen from a 1PP, rated pain and touch valence appropriately, and more intense than the neutral ones. Distinct EEG patterns emerged across early (N2, early posterior negativity, EPN), late (late positive potential, LPP) event-related potentials, and EEG power. The N2 and EPN components showed greater amplitudes for pain and pleasure than neutral stimuli, particularly in 1PP. The LPP component exhibited lower amplitudes for pleasure than pain and neutral stimuli. Further, theta-band power increased, and alpha power decreased for pain and pleasure stimuli viewed from a 1PP versus a 3PP perspective. In the ultra-late time window, we observed decreased theta, alpha, and beta-band power specifically associated with pleasure stimuli. Our study provides novel evidence that perspective-taking modulates the temporal dynamics of vicarious pain and pleasure.

neuroscience↗

bioRxiv2022

Anti-HVEM mAb therapy improves antitumoral immunity both in vitro and in vivo, in a novel transgenic mouse model expressing human HVEM and BTLA molecules challenged with HVEM expressing tumors

BackgroundTNFRF-14/HVEM is the ligand for BTLA and CD160 negative immune co-signaling molecules as well as viral proteins. Its expression is dysregulated with an overexpression in tumors and a connection with tumors of adverse prognosis. MethodsWe developed C57BL/6 mouse models co-expressing human huBTLA and huHVEM as well as antagonistic monoclonal antibodies (mAbs) that completely prevent the interactions of HVEM with its ligands. ResultsHere, we show that the anti-HVEM18-10 mAb increases primary human {beta}-T cells activity alone (CIS-activity) or in the presence of HVEM-expressing lung or colorectal cancer cells in vitro (TRANS-activity). Anti-HVEM18-10 synergizes with anti-PD-L1 mAb to activate T cells in the presence of PDL-1 positive tumors, but is sufficient to trigger T cell activation in the presence of PD-L1 negative cells. In order to better understand HVEM18-10 effect in vivo and especially disentangle its CIS and TRANS effects, we developed a knock-in (KI) mouse model expressing human BTLA (huBTLA+/+) and a KI mouse model expressing both human BTLA and human HVEM (huBTLA+/+ /huHVEM+/+ (DKI)). In vivo pre-clinical experiments performed in both mouse models showed that HVEM18-10 treatment was efficient to decrease human HVEM+ tumor growth. In the DKI model, anti-HVEM 18-10 treatment induces a decrease of exhausted CD8+ T cells and regulatory T cells and an increase of Effector memory CD4+ T cells within the tumor. Interestingly, mice which completely rejected tumors ({+/-} 20%) did not develop tumors upon re-challenge in both settings, therefore showing a marked T cell-memory phenotype effect. ConclusionsAltogether, our preclinical models validate anti-HVEM18-10 as a promising therapeutic antibody to use in clinics as a monotherapy or in combination with existing immunotherapies (anti-PD1/anti-PDL-1/anti-CTLA-4).

immunology↗