Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

The effects of neuroleptics on facial action in schizophrenic patients

This paper describes the influence of neuroleptic therapy on facial action in drug-naive schizophrenics. In a comparative study of medicated and unmedicated schizophrenic patients, the coordinates of 12 small light-reflecting points, attached to subjects' faces, were computer-recorded and analyzed automatically during a semistandardized clinical interview. In addition, facial activity in videotaped interviews was coded using the Facial Action Coding System (FACS). Each sample group comprised of eight patients with the DSMIII- R diagnostic criteria "schizophrenia" or "schizophreniform disorder". Subjects were studied on two occasions, one shortly after admission to the hospital, the other three weeks later. Group I was unmedicated during the first session, whereas group2 was medicated throughout the study. Three weeks after the start of medication, at the second interview, both recording methods showed a reduction in facial activity and facial expression across all subjects in group 1. The facial action of patients in group2, however, remained unchanged.Ziel der vorliegenden Arbeit war die Untersuchung des Einflusses von Neuroleptika auf die Mimik von unmedizierten schizophrenen Patienten. Wiihrend eines halbstandardisierten klinischen Interviews worde die Beweglichkeit von zwolf kleinen, licht-reflektierenden Punkten, die in das Gesicht von medizierten und unmedizierten schizophrenen Patienten geklebt worden, automatisch im Zeitverlauf gemessen. Erganzend wurde der mirnische Ausdruck mit dem Facial Action Coding System (FACS) kodiert, wofiir die Patienten gleichzeitig mit Video aufgenommen worden. Jede der beiden Gruppen bestand aus acht Patienten mit den DSM-IIIR- Diagnosen "Schizophrenie" oder "Schizophrenieforme Storung". Die Patienten worden einmal direkt nach der stationaren Aufnahme und ein zweites Mal nach drei Wochen untersucht. Die Patienten der ersten Gruppe waren zum ersten Zeitpunkt nicht mit Neuroleptika mediziert, wiihrend die der zweiten Gruppe schon zu diesem Zeitpunkt entsprechende Medikamente einnahmen. Es konnte eine Reduktion der mimischen Beweglichkeit des gesamten Gesichtes im Sinne einer neuroleptisch bedingten Hypornimie der primiir Neuroleptika-unbehandelten Patienten bei der zweiten Untersuchung beobachtet werden. Die andere Gruppe Schizophrener, die zu beiden Zeitpunkten mit Neuroleptika behandelt waren, zeigte keine Veriinderung in ihrer mimischen Beweglichkeit

The adenosine pathway in immuno-oncology

Cancer immunotherapy based on immune-checkpoint inhibition or adoptive cell therapy has revolutionized cancer care. Nevertheless, a large proportion of patients do not benefit from such treatments. Over the past decade, remarkable progress has been made in the development of ‘next-generation’ therapeutics in immuno-oncology, with inhibitors of extracellular adenosine (eADO) signalling constituting an expanding class of agents. Induced by tissue hypoxia, inflammation, tissue repair and specific oncogenic pathways, the adenosinergic axis is a broadly immunosuppressive pathway that regulates both innate and adaptive immune responses. Inhibition of eADO-generating enzymes and/or eADO receptors can promote antitumour immunity through multiple mechanisms, including enhancement of T cell and natural killer cell function, suppression of the pro-tumourigenic effects of myeloid cells and other immunoregulatory cells, and promotion of antigen presentation. With several clinical trials currently evaluating inhibitors of the eADO pathway in patients with cancer, we herein review the pathophysiological function of eADO with a focus on effects on antitumour immunity. We also discuss the treatment opportunities, potential limitations and biomarker-based strategies related to adenosine-targeted therapy in oncology.SCOPUS: er.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Adenosine Signaling in the Tumor Microenvironment

Adenosine, deriving from ATP released by dying cancer cells and then degradated in the tumor environment by CD39/CD73 enzyme axis, is linked to the generation of an immunosuppressed niche favoring the onset of neoplasia. Signals delivered by extracellular adenosine are detected and transduced by G-protein-coupled cell surface receptors, classified into four subtypes: A1, A2A, A2B, and A3. A critical role of this nucleoside is emerging in the modulation of several immune and nonimmune cells defining the tumor microenvironment, providing novel insights about the development of novel therapeutic strategies aimed at undermining the immune-privileged sites where cancer cells grow and proliferate