RESUMEN
Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous type of non-Hodgkin lymphoma (NHL) that, in general, is associated with a poor clinical outcome. Therefore, a current major challenge is the discovery of new prognostic tools for this disease. In the present study, a cohort of 122 patients with PTCL was collected from a multicentric T-cell lymphoma consortium (TENOMIC). We analyzed the expression of 80 small nucleolar RNAs (snoRNAs) using high-throughput quantitative PCR. We demonstrate that snoRNA expression analysis may be useful in both the diagnosis of some subtypes of PTCL and the prognostication of both PTCL-not otherwise specified (PTCL-NOS; n = 26) and angio-immunoblastic T-cell lymphoma (AITL; n = 46) patients treated with chemotherapy. Like miRNAs, snoRNAs are globally down-regulated in tumor cells compared with their normal counterparts. In the present study, the snoRNA signature was robust enough to differentiate anaplastic large cell lymphoma (n = 32) from other PTCLs. For PTCL-NOS and AITL, we obtained 2 distinct prognostic signatures with a reduced set of 3 genes. Of particular interest was the prognostic value of HBII-239 snoRNA, which was significantly over-expressed in cases of AITL and PTCL-NOS that had favorable outcomes. Our results suggest that snoRNA expression profiles may have a diagnostic and prognostic significance for PTCL, offering new tools for patient care and follow-up.
Asunto(s)
Perfilación de la Expresión Génica , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/genética , ARN Nucleolar Pequeño/genética , Anciano , Anciano de 80 o más Años , Ciclo Celular/genética , Proliferación Celular , Análisis por Conglomerados , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Linfoma de Células T Periférico/mortalidad , Masculino , Persona de Mediana Edad , PronósticoAsunto(s)
Biomarcadores de Tumor/genética , Genes de las Cadenas Pesadas de las Inmunoglobulinas/genética , Leucemia Linfocítica Crónica de Células B/genética , Mutación , ARN Nucleolar Pequeño/genética , Anciano , Femenino , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Región Variable de Inmunoglobulina/genética , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , ARN Neoplásico/genéticaRESUMEN
Rituximab (RTX, anti-CD20 antibody) combined with chemotherapy is currently standard treatment for chronic lymphocytic leukemia (CLL). Serum level of IL-8 is a prognostic factor for CLL that correlates with disease stage. We investigated whether endogenous IL-8 affects RTX or Obinutuzumab (GA101) B-leukemic depletion mediated by natural killers (NK). Using whole peripheral blood lymphocytes from untreated CLL patients, RTX, but most significantly GA101, were effective in B-cell depletion and NK activation. IL-8 inhibition completely inhibited B-cell depletion by RTX and reduced GA101-induced B-cell depletion. Altogether results underline IL-8 as an endogenous NK co-activator and confirm GA101 therapeutic potential for CLL treatment.
Asunto(s)
Antígenos CD20/inmunología , Linfocitos B/inmunología , Interleucina-8/fisiología , Células Asesinas Naturales/inmunología , Leucemia Linfocítica Crónica de Células B/inmunología , Depleción Linfocítica , Receptores de IgG/agonistas , Anticuerpos Monoclonales/inmunología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , HumanosRESUMEN
Tumor-intrinsic immuno-resistance is a prerequisite for emergence of follicular lymphomas. Here we show that in vitro, such cells are more resistant to immune cytolysis when grown as follicle-mimicking tridimensional aggregates than when grown as cell suspensions. So in patients, this innate adaptation to tumor immunity might precede its selective pressure.