Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

Propuesta de modelo de atención a la enfermedad de Huntington y demencias de inicio precoz en el marco de las enfermedades raras / No disponible

El Servicio Catalán de la Salud (CatSalut) ante la complejidad que conlleva la atención, seguimiento y cuidado de los pacientes con una o más de las llamadas enfermedades minoritarias o raras (ER) ha diseñado una estrategia que tiene entre otros instrumentos un Modelo de atención integral a las enfermedades minoritarias que lo facilite. La Enfermedad de Huntington (EH) así como las demencias de inicio precoz (DIP), demencias primarias o adquiridas en adultos jóvenes, requieren de una atención y seguimiento continuo, específico y transversal para cubrir la necesidades que van apareciendo y pluridisciplinar por la variedad de profesionales que los tendrán que atender en diferentes estadios de la enfermedad. Esta propuesta de modelo basado en los ejes principales del Modelo de atención de las ER y personalizado a partir de las características clínicas y evolutivas de los pacientes con EH o DIP, quiere aportar criterios que faciliten la creación y funcionamiento de una red asistencial efectiva para las necesidades de pacientes y familiares y a la vez eficiente mejorando la utilización de todos los recursos disponibles

The Catalan Health Service (CatSalut) to the complexity involved in attention, monitoring and care of patients with one or more of the so-called minority or rare diseases (RD) has designed a strategy that has inter alia a Model of Care comprehensive minority diseases that facilitate. Huntington 's disease (HD) and early-onset dementia (EOD), that's primary dementia or acquired in young adults, require continuous attention, specific and cross- track to meet the needs that are appearing and the variety of multidisciplinary professionals who are required to attend at different stages of the disease. This proposed model based on the principal axes of Care Model RD and customized from the clinical and developmental characteristics of patients with HD or EOD, wants to provide criteria to facilitate the creation and operation of an effective care network for needs of patients and families and improving both efficient use of all available resources