Prognostic Gene Expression, Stemness and Immune Microenvironment in Pediatric Tumors

Simple Summary Tumors in children and young adults are rare and diagnostically distinct from those occurring in older patients. They frequently arise from developing cells, resembling stem cells, which may explain some of the clinical and biologic differences observed. The aim of this retrospective transcriptome study was to investigate the prognostic landscape, immune tumor microenvironment (TME) and stemness in a cohort of 4068 transcriptomes of such tumors. We find that patients' prognosis correlates with distinct gene expression patterns similar to adult tumor types. Stemness defined by a computational stemness score (mRNAsi) correlates with clinical and molecular parameters that is distinct for each tumor type. In Wilms tumors that recapitulate normal kidney development microscopically, stemness correlates with distinct patterns of immune cell infiltration by transcriptome analysis and by cell localization in tumor tissue. Pediatric tumors frequently arise from embryonal cells, often displaying a stem cell-like (small round blue) morphology in tissue sections. Because recently stemness has been associated with a poor immune response in tumors, we investigated the association of prognostic gene expression, stemness and the immune microenvironment systematically using transcriptomes of 4068 tumors occurring mostly at the pediatric and young adult age. While the prognostic landscape of gene expression (PRECOG) and infiltrating immune cell types (CIBERSORT) is similar to that of tumor entities occurring mainly in adults, the patterns are distinct for each diagnostic entity. A high stemness score (mRNAsi) correlates with clinical and morphologic subtype in Wilms tumors, neuroblastomas, synovial sarcomas, atypical teratoid rhabdoid tumors and germ cell tumors. In neuroblastomas, a high mRNAsi is associated with shortened overall survival. In Wilms tumors a high mRNAsi correlates with blastemal morphology, whereas tumors with predominant epithelial or stromal differentiation have a low mRNAsi and a high percentage of M2 type macrophages. This could be validated in Wilms tumor tissue (n = 78). Here, blastemal areas are low in M2 macrophage infiltrates, while nearby stromal differentiated areas contain abundant M2 macrophages, suggesting local microanatomic regulation of the immune response

The development of a compact millimeter wave scanning system

The following paper describes the development of an autonomous and compact millimeter wave scanning measurement system (SAMMI - Stand Alone Millimeter wave Imager) which works in the W-Band (CW@78GHz). SAMMI® was developed to demonstrate the high potential and usability of the millimeter wave region for material classification[1]

A Population of Murine γδ T Cells That Recognize an Inducible MHC Class Ib Molecule

Although γδ T cells are implicated in regulating immune responses, γδ T cell–ligand pairs that could mediate such regulatory functions have not been identified. Here, the expression of the major histocompatibility complex (MHC) class Ib T22 and the closely related T10 molecules is shown to be activation-induced, and they confer specificity to about 0.4% of the γδ T cells in normal mice. Thus, the increased expression of T22 and/or T10 might trigger immunoregulatory γδ T cells during immune responses. Furthermore, the fast on-rates and slow off-rates that characterize this receptor/ligand interaction would compensate for the low ligand stability and suggest a high threshold for γδ T cell activation.</jats:p

A blood-borne antigen induces rapid T–B cell contact: a potential mechanism for tolerance induction

Understanding the difference between the development of a productive T-cell response and tolerance is central to discerning how the immune system functions. Intravenous injection of soluble protein is thought to mimic the presentation of self-serum and orally introduced antigens. It is generally toleragenic. The current view is that this outcome reflects the failure of ‘immunogenic’ dendritic cells to relocate to the T-cell zone of the secondary lymphoid tissues. Here, using a peptide/I-E(k) tetramer and antibodies to stain splenic sections, we showed that antigen-specific T cells were activated in the spleen within hours of injection or feeding of protein. The activated T cells were found to be located at the T–B junction, the bridging zone and the B-cell area, interacting directly with B cells. In addition, B cells gain the ability to present antigen. Our results suggest a way for T cells to be stimulated by blood-borne antigen presented by naïve B cells, a potential mechanism of tolerance induction

Primary intrahepatic mesotheliomas: A case presentation and literature review

Introduction Primary Intrahepatic mesotheliomas are malignant tumors arising from the mesothelial cell layer covering Glisson\u27s capsule of the liver. They are exceedingly rare with only fourteen cases reported in the literature. They have nonspecific signs and symptoms and need a high index of suspicion and an extensive workup prior to surgery. Surgery remains the mainstay of treatment. Presentation of case 48 year old male presented with a 3 months history of abdominal pain, productive cough, anemia and weight loss. He had no history of asbestos exposure. A computed tomography scan and magnetic resonance study demonstrated a heterogeneous subscapular mass within the dome of the right hepatic lobe measuring 11.3 × 6.1 cm involving the diaphragm. Combined resection of the liver and diaphragm was performed to achieve negative margins. Pathology demonstrated an epithelioid necrotic intrahepatic mesothelioma that stained positive for calretinin, CK AE1/AE3, WT-1, D2-40 and CK7. Discussion Primary intrahepatic mesotheliomas originate from the mesothelial cells lining Glisson\u27s capsule of the liver. They predominantly invade the liver but may also abut or involve the diaphragm. Surgery should include a diagnostic laparoscopy to rule out occult disease or diffuse peritoneal mesothelioma. Complete resection with negative margins should be attempted while maintaining an adequate future liver remnant. Attempts at dissecting the tumor off the involved diaphragm will result in excessive bleeding and may leave residual disease behind. Conclusion Intrahepatic mesotheliomas are rare peripherally-located malignant tumors of the liver. They require a high index of suspicion and a comprehensive workup prior to operative intervention