Epithelial ovarian cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells

IntroductionDespite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity.MethodsIn this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs).ResultsActivated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature.ConclusionThese data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches

Hallazgos citogenéticos en los pacientes de la Unidad de Genética Médica de la Universidad de Los Andes en Mérida, Venezuela

El siguiente estudio tiene por finalidad identificar los hallazgos citogenéticos en los pacientes de la Unidad de Genética Médica de la Universidad de Los Andes, en Mérida, Venezuela, para determinar la prevalencia y tipo de alteraciones cromosómicas. Se realizó un estudio observacional, descriptivo y de corte transversal, en los pacientes evaluados desde enero de 2005 a enero de 2012. El estudio citogenético fue realizado por técnica convencional de banda G. De un total de 716 estudios citogenéticos realizados, 113 (15,78%) presentaron algún tipo de alteración de los cromosomas autosómicos y la trisomía 21 fue la más frecuente con 95 (84,07%); 71 (9,92%) de los cromosomas sexuales y la monosomía del X fue la más común con 67 (94,37%). La trisomía 21 constituye el principal tipo de alteración cromosómica en este estudio y los revisados, siendo la trisomía libre la forma más común. La monosomía del X constituye la segunda anormalidad cromosómica y la primera de los cromosomas sexuales, resaltando la alta frecuencia de mosaicismo con una línea celular con monosomía del X y otra línea celular normal. Es pertinente difundir la importancia del análisis citogenético en la práctica médica, como recurso útil en estudio de pacientes con alteraciones cromosómicas. Cytogenetic findings in the patients of the Unit of Medical Genetics University of Los Andes, in Mérida, Venezuela Abstract The following study aims to identify the cytogenetic findings in the patients of the Unit of Medical Genetics of the University of Los Andes in Merida, Venezuela to determine the prevalence and type of chromosomal abnormalities. An observational, descriptive and cross-sectional study was performed in the patients evaluated from january 2005 to january 2012. The cytogenetic study was realized by conventional technique G-banding. A total of 716 of cytogenetic studies performed, 113 (15,78%) had some type of alteration of autosomal chromosomes and trisomy 21 was the most frequent with 95 (84,07%); 71 (9,92%) of the sex chromosomes and the X monosomy was most common with 67 (94,37%). Trisomy 21 is the main type of chromosomal abnormality in this study and revised, with free trisomy the most common form. The X monosomy is the second and the first abnormality of the sex chromosomes, with emphasis the high frequency of mosaicism with a cell line with monosomy for the X and one normal cell line. It is pertinent to spread the importance of cytogenetic analysis in medical practice, as a useful resource in the study of patients with chromosomal alterations

Características clínicas y citogenéticas en el síndrome de Wolf-Hirschhorn. Serie de casos

Resumen (español) El síndrome de Wolf-Hirschhorn es una entidad genética producida por una deleción parcial que abarca la región distal del brazo corto del cromosoma 4 (4p16.3). Las manifestaciones más frecuentes son anomalías craneofaciales, retraso psicomotor y alteraciones neurológicas. La incidencia estimada es de 1 en 50.000 nacimientos, aunque hay un subdiagnóstico de esta entidad. El objetivo de este estudio es describir cuatro casos clínicos del síndrome de Wolf-Hirschhorn con descripción específica de los hallazgos clínicos y citogenéticos Abstract (english) Wolf-Hirschhorn syndrome is a genetic entity produced by a partial deletion spanning the distal short arm of chromosome 4 (4p16.3). The most common manifestations are craniofacial anomalies, psychomotor retardation and neurological disorders. The estimated incidence is 1 in 50,000 births, although there is an underdiagnosis of this entity. The aim of this study is to describe four clinical cases of Wolf-Hirschhorn syndrome with specific description of clinical and cytogenetic finding