Immune Response Modulation by Tumor-Secreted Glycosphingolipids

Although originally considered merely structural components of cellular membranes, glycosphingolipids (GSL) arenow recognized as having critical effects on cellular physiology, including proliferation, differentiation, viraltransformation and ontogenesis. In addition, a vast majority of human cancers have modified GSL compositioncompared to parental normal cells. These modifications may contribute to both tumor survival and exert strikingeffects on anti-tumor immunity. In this review, we discuss mechanisms of immune modulation by tumor-secreted GSL.Fil: Lardone, Ricardo Dante. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Cely, Ingrid. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados UnidosFil: Sieling, Peter A.. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados UnidosFil: Lee, Delphine. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados Unido

Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors.

The microbiome impacts human health and disease. Until recently, human breast tissue and milk were presumed to be sterile. Here, we investigated the presence of microbes in the nipple aspirate fluid (NAF) and their potential association with breast cancer. We compared the NAF microbiome between women with a history of breast cancer (BC) and healthy control women (HC) using 16S rRNA gene amplicon sequencing. The NAF microbiome from BC and HC showed significant differences in community composition. Two Operational Taxonomic Units (OTUs) showed differences in relative abundances between NAF collected from BC and HC. In NAF collected from BC, there was relatively higher incidence of the genus Alistipes. By contrast, an unclassified genus from the Sphingomonadaceae family was relatively more abundant in NAF from HC. These findings reflect the ductal source DNA since there were no differences between areolar skin samples collected from BC and HC. Furthermore, the microbes associated with BC share an enzymatic activity, Beta-Glucuronidase, which may promote breast cancer. This is the first report of bacterial DNA in human breast ductal fluid and the differences between NAF from HC and BC. Further investigation of the ductal microbiome and its potential role in breast cancer are warranted

Differential Effect of TLR2 and TLR4 on the Immune Response after Immunization with a Vaccine against Neisseria meningitidis or Bordetella pertussis

Neisseria meningitidis and Bordetella pertussis are Gram-negative bacterial pathogens that can cause serious diseases in humans. N. meningitidis outer membrane vesicle (OMV) vaccines and whole cell pertussis vaccines have been successfully used in humans to control infections with these pathogens. The mechanisms behind their effectiveness are poorly defined. Here we investigated the role of Toll-like receptor (TLR) 2 and TLR4 in the induction of immune responses in mice after immunization with these vaccines. Innate and adaptive immune responses were compared between wild type mice and mice deficient in TLR2, TLR4, or TRIF. TRIF-deficient and TLR4-deficient mice showed impaired immunity after immunization. In contrast, immune responses were not lower in TLR2−/− mice but tended even to be higher after immunization. Together our data demonstrate that TLR4 activation contributes to the immunogenicity of the N. meningitidis OMV vaccine and the whole cell pertussis vaccine, but that TLR2 activation is not required