Murine Models of B-Cell Lymphomas: Promising Tools for Designing Cancer Therapies

Human B-cell lymphomas, the fourth most common hematologic malignancy, are currently the subject of extensive research. The limited accessibility of biopsies, the heterogeneity among patients, and the subtypes of lymphomas have necessitated the development of animal models to decipher immune escape mechanisms and design new therapies. Here, we summarize the cell lines and murine models used to study lymphomagenesis, the lymphoma microenvironment, and the efficacy of new therapies. These data allow us to understand the role of the immune system in the fight against tumors. Exploring the advantages and limitations of immunocompetent versus immunodeficient models improves our understanding of the molecular and cellular mechanisms of tumor genesis and development as well as the fundamental processes governing the interaction of tumors and their host tissues. We posit that these basic preclinical investigations will open up new and promising approaches to designing better therapies

Th17 Cells Are Involved in the Local Control of Tumor Progression in Primary Intraocular Lymphoma

BACKGROUND: Th17 cells play an important role in the pathogenesis of many autoimmune diseases, but despite some reports of their antitumor properties, too little is known about their presence and role in cancers. Specifically, knowledge is sparse about the relation of Th17 to lymphoma microenvironments and, more particularly, to the microenvironment of primary intraocular B-cell lymphoma (PIOL), an aggressive lymphoma with a poor prognosis. METHODS AND PRINCIPAL FINDINGS: In this work, we investigated the presence of Th17 cells and their related cytokines in a syngeneic model of PIOL, a subtype of non-Hodgkin lymphoma. The very small number of lymphocytes trafficking in normal eyes, which represent a low background as compared to tumor-bearing eyes, allows us to develop the present model to characterize the different lymphocyte subsets present when a tumor is developing. IL-21 mRNA was expressed concomitantly with IL-17 mRNA in tumor-bearing eyes and intracellular expression of IL-17A and IL-21 in infiltrating CD4(+) T lymphocytes. Interestingly, IL-17A production by T cells was negatively correlated with tumor burden. We also showed that IL-21 but not IL-17 inhibits tumor cell proliferation in vitro. CONCLUSIONS: These data demonstrate that IL-17A and IL-21-producing CD4(+) T cells, referred as Th17 cells, infiltrate this tumor locally and suggest that Th17-related cytokines may counteract tumor progression via IL-21 production. Thus, Th17 cells or their related cytokines could be considered to be a new therapeutic approach for non-Hodgkin B-cell lymphomas, particularly those with an ocular localization

Etude du microenvironnement cellulaire et moléculaire des lymphomes B intra-oculaires (mise au point d'un modèle murin et étude du rôle des lymphocytes T régulateurs naturels)

Les lymphomes intraoculaires primitifs (PIOL) constituent une pathologie tumorale intraoculaire maligne mal connue et de pronostic extrêmement sévère. De nombreux facteurs expliquent le pronostic sombre des lymphomes intra-oculaire mais le plus important d entre eux est l absence de modèle animal permettant de comprendre les mécanismes physiopathologique de la maladie. L oeil, de part son anatomie et sa physiologie constitue un site immunologiquement privilégié au sein duquel la réponse anti-tumorale est différente de celle observée en périphérie. Ce travail de thèse à pour but de développer le premier modèle murin de lymphome B intraoculaire chez un hôte immunocompétent, et d étudier l environnement moléculaire et cellulaire de la tumeur. L étude de ce microenvironnement tumoral a permis de mettre en évidence un milieu suppresseur tout à fait particulier, propice au développement tumoral, comprenant de l interleukine-10, ainsi qu un très fort enrichissement en cellules T régulatrices naturelles et induites. Cet environnement tumoral particulier se traduit par une inhibition partielle des lymphocytes T infiltrant la tumeur dont le profil cytokinique Th1 est incomplet. L étude du microenvironnement moléculaire et cellulaire de la tumeur a permis de déterminer les grands axes de futures stratégies thérapeutiques qui devront cibler non seulement la tumeur elle-même, mais également son micro-environnement particulier. Ces conclusions ont abouti au développement d un protocole de recherche clinique dans le but d évaluer l efficacité de l un de ces traitements (anticorps monoclonaux anti-CD20) chez l hommePARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Prise en charge diagnostique et thérapeutique du syndrome de Vogt-Koyanagi-Harada

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Apport des techniques moléculaires dans la pratique clinique chez les patients atteints de lymphome vitréo-rétinien primitif

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Retinal microvasculature in pituitary adenoma patients: is optical coherence tomography angiography useful?

Pituitary adenoma (PA) is one of the most common causes of benign intracranial masses. Optical coherence tomography angiography (OCTA) is an emerging, non-invasive method to study the microvasculature of the macula and the optic nerve head. The aim of this study was to assess the vasculature changes in the peripapillary and macular areas associated with PA using OCTA

Ophthalmological Spectrum of Locked-In Syndrome

"Although a few authors have reported abnormal eye movements in Locked in syndrome (LIS), there is no study focusing on the large spectrum of ophthalmological manifestations of LIS and their consequences on the visual function. The aim of this study is to describe the range of ophthalmological manifestations observed in patients with LIS, and to evaluate their visual impairment.

Perspectives for immunotherapy in noninfectious immune mediated uveitis

International audienc