Le temple du DA III de la déesse Ninhursag à Mari : les dépôts votifs du Lieu Très Saint

La campagne de fouille menée en 1997 dans le temple archaïque attribué à la déesse Ninhursag, en particulier dans la partie occidentale et centrale du Lieu Très Saint, a permis la découverte d’un important matériel votif, dont le caractère exceptionnel justifie la publication dans ce volume, sans attendre le rapport préliminaire d’ensemble de cette campagne (fig. 1). Une partie des objets retrouvés a d’ailleurs déjà été offerte au public à l’occasion d’une exposition organisée par le musée de..

Mari : rapport préliminaire sur la campagne de 1994

La XXXIe campagne de fouille à Tell Hariri s’est tenue sur le site du 1er au 30 novembre 1994, le séjour en Syrie de la plupart des membres de la Mission ayant eu lieu entre le 26 octobre et le 4 décembre. Malgré les mauvaises conditions climatiques, tous les objectifs visés ont été atteints. Deux chantiers seulement ont été en activité : F et l’espace central de l’Enceinte Sacrée. Outre son directeur, l’équipe était composée de : Emmanuelle Capet et Béatrice Muller, archéologues ; Marie-Fran..

Mari : rapport préliminaire sur la campagne de 1993

La mission est arrivée en ordre dispersé en Syrie le 16 septembre ; le 19, la maison de fouille était ouverte et les travaux sur le terrain ont pu commencer sans tarder. Le 6 novembre, les derniers travaux ont été conduits sur le chantier et la dispersion des membres a commencé. L’équipe était composée, outre son directeur, de six archéologues de terrain – D. Beyer, E. Capet, P. Gontier, M. Schneider, A. Liégey, I. Weygand –, de quatre stagiaires – F. Vergeot, D. Bonneterre, A. et J. Hurstel ..

HEV-associated dendritic cells are observed in metastatic tumor-draining lymph nodes of cutaneous melanoma patients with longer distant metastasis-free survival after adjuvant immunotherapy

Introduction: Tissue biomarkers that aid in identifying cutaneous melanoma (CM) patients who will benefit from adjuvant immunotherapy are of crucial interest. Metastatic tumor-draining lymph nodes (mTDLN) are the first encounter site between the metastatic CM cells and an organized immune structure. Therefore, their study may reveal mechanisms that could influence patients´ outcomes. Methods: Twenty-nine stage-III CM patients enrolled in clinical trials to study the vaccine VACCIMEL were included in this retrospective study. After radical mTDLN dissection, patients were treated with VACCIMEL (n=22) or IFNα-2b (n=6), unless rapid progression (n=1). Distant Metastasis-Free Survival (DMFS) was selected as an end-point. Two cohorts of patients were selected: one with a good outcome (GO) (n=17; median DMFS 130.0 months), and another with a bad outcome (BO) (n=12; median DMFS 8.5 months). We analyzed by immunohistochemistry and immunofluorescence the expression of relevant biomarkers to tumor-cell biology and immune cells and structures in mTDLN, both in the tumor and peritumoral areas. Results: In BO patients, highly replicating Ki-67+ tumor cells, low tumor HLA-I expression and abundant FoxP3+ lymphocytes were found (p=0.037; p=0.056 and p=0.021). In GO patients, the most favorable biomarkers for prolonged DMFS were the abundance of peri- and intra-tumoral CD11c+ cells (p=0.0002 and p=0.001), peri-tumoral DC-LAMP+ dendritic cells (DCs) (p=0.001), and PNAd+ High Endothelial Venules (HEVs) (p=0.004). Most strikingly, we describe in GO patients a peculiar, heterogeneous structure that we named FAPS (Favoring Antigen-Presenting Structure), a triad composed of DC, HEV and CD62L+ naïve lymphocytes, whose postulated role would be to favor tumor antigen (Ag) priming of incoming naïve lymphocytes. We also found in GO patients a preferential tumor infiltration of CD8+ and CD20+ lymphocytes (p=0.004 and p=0.027), as well as peritumoral CD20+ aggregates, with no CD21+ follicular dendritic cells detected (p=0.023). Heterogeneous infiltration with CD64+CD68-CD163-, CD64+CD68+CD163- and CD64+CD68+CD163+ macrophages were observed in both cohorts. Discussion: The analysis of mTDLN in GO and BO patients revealed marked differences. This work highlights the importance of analyzing resected mTDLN from CM patients and suggests a correlation between tumor and immune characteristics that may be associated with a spontaneous or vaccine-induced long DMFS. These results should be confirmed in prospective studies.Fil: Bravo, Alicia Inés. Fundación Instituto Leloir; ArgentinaFil: Aris, Mariana. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Marylou Panouillot. Sorbonne University; FranciaFil: Porto, Martina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Dieu Nosjean, Marie Caroline. Sorbonne University; FranciaFil: Teillaud, Jean Luc. Sorbonne University; FranciaFil: Barrio, Maria Marcela. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mordoh, José. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Fundación Instituto Leloir; Argentin

Mari : rapport préliminaire sur la campagne de 1995

Cette campagne, la XXXIIe conduite sur le tell Hariri, ne pouvait être que de faible durée compte tenu des conditions générales. Alors que six à sept semaines de fouille avaient été primitivement prévues, il a fallu rabattre les prétentions à quatre semaines et demie pour des raisons administratives et surtout financières. Parvenue à Damas le 27 septembre, la Mission s’est trouvée réunie à Mari le 29 avec l’arrivée de la voiture venue de France par la route. Commencé le 30 septembre au matin,..

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

International audienceThe tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of “hot” tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an “anti-tumor school” and an “antibody factory” to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy

Early EEG for Prognostication Under Venoarterial Extracorporeal Membrane Oxygenation

International audienceBackground/objectives: Tools for prognostication of neurologic outcome of adult patients under venoarterial ECMO (VA-ECMO) have not been thoroughly investigated. We aimed to determine whether early standard electroencephalography (stdEEG) can be used for prognostication in adults under VA-ECMO.Methods: Prospective single-center observational study conducted in two intensive care units of a university hospital, Paris, France. Early stdEEG was performed on consecutive adult patients treated with VA-ECMO for refractory cardiogenic shock or refractory cardiac arrest. The association between stdEEG findings and unfavorable outcome was investigated. The primary endpoint was 28-day mortality. The secondary endpoint was severe disability or death at 90 days, defined by a score of 4-6 on the modified Rankin scale.Results: A total of 122 patients were included, of whom 35 (29%) received cardiopulmonary resuscitation before VA-ECMO cannulation. Main stdEEG findings included low background frequency ≤ 4 Hz (n = 27, 22%) and background abnormalities, i.e., a discontinuous (n = 20, 17%) and/or an unreactive background (n = 12, 10%). Background abnormalities displayed better performances for prediction of unfavorable outcomes, as compared to clinical parameters at time of recording. An unreactive stdEEG background in combination with a background frequency ≤ 4 Hz had a false positive rate of 0% for prediction of unfavorable outcome at 28 days and 90 days, with sensitivities of 8% and 6%, respectively. After adjustment for confounders, a lower background frequency was independently associated with unfavorable outcome at 28 days (adjusted odds ratio per 1-Hz increment, 95% CI 0.71, 0.52-0.97), whereas no such independent association was observed at 90 days.Conclusion: Standard EEG abnormalities recorded at time of VA-ECMO initiation are predictive of unfavorable outcomes. However, the low sensitivity of these parameters highlights the need for a multimodal evaluation for improving management of care and prognostication

Akh Purattim 2

Akh Purattim ou « les rives de l’Euphrate » est une des expressions utilisées au xviiie siècle av. J.-C. pour désigner le royaume de Mari, qui s'étendait de la confluence du Khabour au verrou de Baghouz, actuellement à la frontière syro-irakienne. La série ainsi dénommée, précisée par son sous-titre « Mémoires d'archéologie et d'histoire régionales interdisciplinaires », est destinée à devenir le point de rencontre des recherches historiques, archéologiques, épigraphiques ou archéométriques sur la région, en faisant en priorité appel aux travaux engagés par les diverses missions, françaises (Mari, Terqa…) et étrangères, en particulier pour la publication de leurs rapports préliminaires. Mais le titre peut également être pris dans une acception géographique beaucoup plus vaste et héberger des études qui s'intéressent le plus largement possible au rôle de cette confluence dans le jeu syro-mésopotamien tout au long de l'Antiquité.Akh Purattim or “the banks of the Euphrates” is one of the expressions used in the 18th century B.C. to designate the kingdom of Mari, which extended from the confluence of the Khabur to the glacial cross cliff of Baghuz, today the Syrian-Iraqi border. The series thus named, defi ned by its subtitle Mémoires d'archéologie et d'histoire régionales interdisciplinaires, is intended to become the meeting point for historical, archaeological, epigraphic and archaeometric research on the region, with priority given to the work conducted by the various missions, French (Mari, Terqa…) as well as foreign, in particular the publication of their preliminary reports. But the title can also include a larger geographic area and cover studies which are concerned as widely as possible with the role of this confl uence in Syro-Mesopotamian history throughout Antiquity

Akh Purattim 1

Akh Purattim ou « les rives de l'Eupkrate » est une des expressions utilisées au xviiie siècle av. J.-C. pour désigner le royaume de Mari, qui s’étendait de la confluence du Khabour au verrou de Bagbouz, actuellement à la frontière syro-irakienne. La série ainsi dénommée, précisée par son sous-titre Mémoires d’archéologie et d’histoire régionales interdisciplinaires, est destinée à devenir le point de rencontre des recherches historiques, archéologiques, épigraphiques ou archéométriques sur la région, en faisant en priorité appel aux travaux engagés par les diverses missions, françaises (Mari, Terqa...) et étrangères, en particulier pour la publication de leurs rapports préliminaires. Mais le titre peut également être pris dans une acception géographique beaucoup plus vaste et héberger des études qui s’intéressent le plus largement possible au rôle de cette confluence dans le jeu syro-mésopotamien tout au long de l’Antiquité.Akh Purattim or “the hanks of the Euphrates is one of the expressions used in the 18th century B.C. to designate the kingdom of Mari, which extended from the confluence of the Khahur to the glacial cross cliff of Baghuz, today the Syrian-Iraqi harder. The series thus named, defined by its subtitle Mémoires darchéologie et d’histoire régionales interdisciplinaires, is intended to become the meeting point for historical, archaeological, epigraphic and archaeometric research on the region, with priority given to the work conducted by the various missions, Trench (Man, Terqa...) as well as foreign, in particular the publication of their preliminary reports. But the title can also include a larger geographic area and cover studies which arc concerned as widely as possible with the role of this confluence in Syro-Mesopotamian history throughout Antiquity