Mayo Clinic Laboratory and Pathology Research Roundup: Dec. 17

By Kelley Luedke • December 17, 2018

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The Research Roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.

Featured Abstract

Phosphorylated RB Promotes Cancer Immunity by Inhibiting NF-κB Activation and PD-L1 Expression

Aberrant expression of programmed death ligand-1 (PD-L1) in tumor cells promotes cancer progression by suppressing cancer immunity. The retinoblastoma protein RB is a tumor suppressor known to regulate the cell cycle, DNA damage response, and differentiation. Mayo Clinic researchers demonstrated that RB interacts with nuclear factor κB (NF-κB) protein p65 and that their interaction is primarily dependent on CDK4/6-mediated serine-249/threonine-252 (S249/T252) phosphorylation of RB. RNA-seq analysis shows that a subset of NF-κB pathway genes, including PD-L1, are selectively upregulated by RB knockdown or CDK4/6 inhibitor. S249/T252-phosphorylated RB inversely correlates with PD-L1 expression in patient samples. Expression of an RB-derived S249/T252 phosphorylation-mimetic peptide suppresses radiotherapy-induced upregulation of PD-L1 and augments therapeutic efficacy of radiation in vivo. The findings reveal a previously unrecognized tumor suppressor function of hyperphosphorylated RB in suppressing NF-κB activity and PD-L1 expression and suggest that the RB-NF-κB axis can be exploited to overcome cancer immune evasion triggered by conventional or targeted therapies. The study was published in Molecular Cell.

Published to PubMed This Week

• • • • • Clinical Validity Assessment of Genes Frequently Tested on Hereditary Breast and Ovarian Cancer Susceptibility Sequencing Panels
          Genetics in Medicine
        • Primary Central Nervous System Vasculitis Mimicking Brain Tumor: Comprehensive Analysis of 13 Cases from a Single Institutional Cohort of 191 Cases
          Journal of Autoimmunity
        • Predictors of Symptomatic Kidney Stone Recurrence after the First and Subsequent Episodes
          Mayo Clinic Proceedings
        • High-Sensitivity Cardiac Troponin I Levels in Normal Pregnancy and When Complicated by Hypertension
          American Journal of Medicine
        • Assessment of Test Performance and Potential for Environmental Contamination Associated with a Point-of-Care Molecular Assay for Group A Streptococcus in an End-User Setting
          Journal of Clinical Microbiology
          
        • KMT2A (MLL) Rearrangements Observed in Pediatric/Young Adult T-Lymphoblastic Leukemia/Lymphoma: A 10-Year Review from a Single Cytogenetic Laboratory
          Genes, Chromosomes and Cancer
          
        • Cloning, Function, and Localization of Human, Canine and Drosophila Zip10 (Slc39a10), a Zn²⁺ Transporter
          American Journal of Physiology-Renal Physiology
        • Utility of Adjuvant Chemotherapy in Patients Receiving Surgery and Adjuvant Radiotherapy for Primary Treatment of Esthesioneuroblastoma
          Head and Neck
          
        • The Prognostic Significance of TERT Promoter Mutations in Meningioma: A Systematic Review and Meta-Analysis
          Journal of Neuro-Oncology
        • Clearance Kinetics of the VGF-Derived Neuropeptide TLQP-21
          Neuropeptides
        • Developing a Process for Returning Medically Actionable Genomic Variants to Latino Patients in a Federally Qualified Health Center
          Public Health Genomics

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.