Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients.

The understanding of the role of B cells in patients with solid tumors remains insufficient. We found that circulating B cells produced TNFα and/or IL-6, associated with unresponsiveness and poor overall survival of melanoma patients treated with anti-CTLA4 antibody. Transcriptome analysis of B cells from melanoma metastases showed enriched expression of inflammatory response genes. Publicly available single B cell data from the tumor microenvironment revealed a negative correlation between TNFα expression and response to immune checkpoint blockade. These findings suggest that B cells contribute to tumor growth via the production of inflammatory cytokines. Possibly, these B cells are different from tertiary lymphoid structure-associated B cells, which have been described to correlate with favorable clinical outcome of cancer patients. Further studies are required to identify and characterize B cell subsets and their functions promoting or counteracting tumor growth, with the aim to identify biomarkers and novel treatment targets

Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 study.

Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18-45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. 26 participants were enrolled (August-September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088-0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/10 <sup>5</sup> CD8+, 95% CI: 0.19-5.13, p = 0.014 and +1.34/10 <sup>5</sup> CD8+, 95% CI: 0.1-7.34, p = 0.024, respectively). Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. Emergex Vaccines Holding Limited

Plasma Dynamics

Contains reports on twenty research projects split into two sections.National Science Foundation (Grant ENG75-06242-A01)U. S. Energy Research and Development Administration (Contract E(11-1)-2766)U. S. Energy Research and Development Administration (Contract E(11-1)-3070

Plasma Dynamics

Contains research objectives and summary of research on twenty-one projects split into three sections, with four sub-sections in the second section and reports on twelve research projects.National Science Foundation (Grant ENG75-06242)U.S. Energy Research and Development Administration (Contract E(11-1)-2766)U.S. Energy Research and Development Agency (Contract E(11-1)-3070)U.S. Energy Research and Development Administration (Contract E(11-1)-3070)Research Laboratory of Electronics, M.I.T. Industrial Fellowshi

Developmental and pathological lymphangiogenesis: from models to human disease.

The lymphatic vascular system, the body's second vascular system present in vertebrates, has emerged in recent years as a crucial player in normal and pathological processes. It participates in the maintenance of normal tissue fluid balance, the immune functions of cellular and antigen trafficking and absorption of fatty acids and lipid-soluble vitamins in the gut. Recent scientific discoveries have highlighted the role of lymphatic system in a number of pathologic conditions, including lymphedema, inflammatory diseases, and tumor metastasis. Development of genetically modified animal models, identification of lymphatic endothelial specific markers and regulators coupled with technological advances such as high-resolution imaging and genome-wide approaches have been instrumental in understanding the major steps controlling growth and remodeling of lymphatic vessels. This review highlights the recent insights and developments in the field of lymphatic vascular biology

Pourquoi les interfaces cerveau-machine marchent-elles mal avec les patient-e-s qui en ont le plus besoin ?

A major objective of Brain-Computer interfaces (BCI) is to restore communication and control in patients with severe motor impairments, like people with Locked-in syndrome. These patients are left only with limited eye and eyelid movements. However, they do not benefit from efficient BCI solutions, yet. Different signals can be used as commands for non-invasive BCI: mu and beta rhythm desynchronization, evoked potentials and slow cortical potentials. Whatever the signal, clinical studies show a dramatic loss of performance in severely impaired patients compared to healthy subjects. Interestingly, the control principle is always the same, namely the replacement of an impossible (overt) movement by a (covert) attentional command. Drawing from the premotor theory of attention, from neuroimaging findings about the functional anatomy of spatial attention, from clinical observations and from recent computational accounts of attention for both action and perception, we explore the hypothesis that these patients undergo negative plasticity that extends their impairment from overt to covert attentional processes