scholarly journals 678 The neonatal Fc receptor is elevated in monocyte-derived immune cells in pancreatic cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A706-A706
Author(s):  
Justin Thomas ◽  
Molly Torok ◽  
Kriti Agrawal ◽  
Trang Vu ◽  
Alyssa Castillo ◽  
...  

BackgroundPancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States with 5-year survival rates below 10%. PDAC is commonly diagnosed after metastasis has occurred and treatment options are limited. Immune checkpoint inhibitor (ICI) monoclonal antibody (mAb) therapy has shown great promise in other cancers, however little efficacy has been observed in patients with PDAC. The protein responsible for recycling IgG based mAb therapeutics like ICIs in the bloodstream, as well as processing peptides for antigen presentation, is the neonatal Fc receptor (FcRn). Little is known about FcRn in cancer, and to our knowledge no characterization of host FcRn, or FcRn extrinsic to tumor cells exists in PDAC patients. We hypothesized that PDAC patients and tumor-bearing animals would have altered FcRn expression by their immune populations compared to their healthy counterparts.MethodsC57BL/6 mice were orthotopically injected with KPC-luc (KrasLSL-G12D, Trp53LSL-R270H, Pdx1-cre) pancreatic tumor cells, and FcRn expression in myeloid-derived splenocytes were analyzed by fluorescence cytometry. Time-of-flight mass cytometry (CyTOF) was utilized to immunophenotype peripheral blood mononuclear cells (PBMCs) of PDAC or non-cancer patients for expression levels of FcRn within these immune populations.ResultsPDAC tumor-bearing mice exhibit altered FcRn expression among myeloid immune cell populations. Mice with pancreatic tumors had elevated expression of FcRn on migratory cDC2 (CD8-CD11b+CD103+CD24++; p = 0.017), monocytic MDSC (CD11b+Ly6G-Ly6C+; p = 0.0023), granulocytic MDSC (CD11b+Ly6G+Ly6C±; p = 0.0542), and cDC2 (CD8-CD11b+CD103-CD24±; p=0.036) cells. PBMCs from non-cancer obese patients (healthy control samples; n=8) and PDAC patients prior to surgical resection (n=13) were subjected to CyTOF analyses. The majority of FcRn expression was concentrated to monocyte (p=0.017), DCs (p=0.017) and MDSC (p=0.012) immune populations. Overall, we observed increased expression of FcRn on myeloid-derived immune populations from patients with PDAC. FcRn expression was elevated in both monocytes and DC populations in PDAC relative to non-cancer PBMCs. Monocytic and granulocytic MDSC from patients with PDAC had significantly elevated FcRn positivity compared to healthy controls (p = 0.034, p = 0.026, respectively).ConclusionsFcRn is upregulated in monocytes, dendritic cells and MDSC immune populations in patients and mice with pancreatic tumors. Future investigations into FcRn function in preclinical models and PDAC patients will hopefully elucidate new mechanisms of ICI resistance and possible alternative approaches for improving immunotherapy efficacy in these patients.Ethics ApprovalAll patients provided voluntary written informed consent (Institutional Review Board protocol: 2010C0051) to participate. The protocols and subsequent amendments were approved by The Ohio State University Institutional Review Board. All animal protocols were approved by the Ohio State University Institutional Animal Care and Use Committee (IACUC) at The Ohio State University (Approved IACUC protocols 2009A0178-R4 and 2017A00000117-R1) and mice were treated in accordance with institutional guidelines for animal care. The Ohio State University Laboratory Animal Shared Resource is an Association for Assessment and Accreditation of Laboratory Animal Care International accredited program that follows Public Health Service policy and guidelines. All other experiments were completed under the research protocols (2014R00000086; 2013R00000056) approved by the Ohio State University Institutional Biosafety Committee.

2016 ◽  
Vol 1 (5) ◽  
pp. 4-12
Author(s):  
David P. Kuehn

This report highlights some of the major developments in the area of speech anatomy and physiology drawing from the author's own research experience during his years at the University of Iowa and the University of Illinois. He has benefited greatly from mentors including Professors James Curtis, Kenneth Moll, and Hughlett Morris at the University of Iowa and Professor Paul Lauterbur at the University of Illinois. Many colleagues have contributed to the author's work, especially Professors Jerald Moon at the University of Iowa, Bradley Sutton at the University of Illinois, Jamie Perry at East Carolina University, and Youkyung Bae at the Ohio State University. The strength of these researchers and their students bodes well for future advances in knowledge in this important area of speech science.


2011 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Alex J Auseon ◽  
Albert J Kolibash ◽  
◽  

Background:Educating trainees during cardiology fellowship is a process in constant evolution, with program directors regularly adapting to increasing demands and regulations as they strive to prepare graduates for practice in today’s healthcare environment.Methods and Results:In a 10-year follow-up to a previous manuscript regarding fellowship education, we reviewed the literature regarding the most topical issues facing training programs in 2010, describing our approach at The Ohio State University.Conclusion:In the midst of challenges posed by the increasing complexity of training requirements and documentation, work hour restrictions, and the new definitions of quality and safety, we propose methods of curricula revision and collaboration that may serve as an example to other medical centers.


2019 ◽  
pp. 113-118

Background Suppression is associated with binocular vision conditions such as amblyopia and strabismus. Commercial methods of testing fusion often only measure central fusion or suppression at near. The purpose of this pilot study was to assess a new iPad picture fusion test that assesses foveal and central fusion at near. Methods Participants aged 5 years and older presenting for eye examination at The Ohio State University College of Optometry were enrolled. Results from visual acuity, dry and wet refraction/retinoscopy, stereopsis and cover testing were recorded from the patient chart. The iPad picture fusion test, Worth four-dot, Worth type test with foveal letter targets, and Polarized four-dot were performed by one examiner in a randomized order at 40 cm. Testing was repeated with the anaglyphic filters reversed. Crosstabulation and McNemar chi-square analysis were used to compare the results between fusion testing devices. Results Of the fifty participants (mean age = 17.5), twelve reported suppression and one reported diplopia. Testability was excellent for all tests (98% to 100%). There were no significant differences between tests in reported results (P ≥ 0.22 for all comparisons). No difference in reported fusion or suppression status was observed with change in orientation of the anaglyphic filters. Six participants reported foveal suppression alone at near which was not identified with Worth four-dot at near. Conclusion The iPad picture fusion test provided excellent testability and agreement with commonly used tests of fusion and allowed testing of both central and foveal fusion at near. Nearly half (46%) of participants with suppression reported foveal suppression, supporting the importance of testing for foveal suppression.


2014 ◽  
Vol 41 (1) ◽  
pp. 61-78 ◽  
Author(s):  
Dale L. Flesher ◽  
Gary J. Previts

George O. May, one of, if not ‘the’ leading spokesman for the American Institute of CPAs for most of his lifetime, was the product of British education and an articled clerkship. This paper reviews the features and information about May's clerkship (indentureship) articles, including aspects of what is now called professional responsibility. Also mentioned are selected highlights and sources related to his career in public accounting, including his ‘cameo’ role at the l904 World Congress of Accountants in St. Louis where he participated with prominent leaders of the emerging United States CPA community, including Staub, Sterrett, Montgomery, and Sells, as well as his countrymen Pixley and Dickinson [Official Record, p. 164]. This study of George O. May's preparation provides details about a relatively unnoticed chapter in the career of an individual who was among the first group of inductees, in l950, along with William A. Paton and Robert H. Montgomery, to the Accounting Hall of Fame at The Ohio State University. Additionally, May's clerkship requirements are indicative of the role of professional responsibility in the decade before the turn of the twentieth century.


2020 ◽  
Vol 41 (S1) ◽  
pp. s409-s409
Author(s):  
Emily Feyes ◽  
Dixie Mollenkopf ◽  
Thomas Wittum ◽  
Dubraska Diaz-Campos ◽  
Rikki Horne

Emily Feyes, The Ohio State University College of Veterinary Medicine; Dixie Mollenkopf, The Ohio State University College of Veterinary Medicine; Thomas Wittum, The Ohio State University College of Veterinary Medicine; Dubraska Diaz-Campos, The Ohio State University College of Veterinary Medicine; Rikki Horne, The Ohio State University College of Veterinary MedicineBackground: The Ohio State University College of Veterinary Medicine (OSU-CVM) Antimicrobial Stewardship Working Group (ASWG) uses monthly environmental surveillance to understand the effectiveness of our veterinary medical center (VMC) infection control and biosecurity protocols in reducing environmental contamination with multidrug resistant organisms. Monthly surveillance allows us to monitor trends in the recovery of these resistant organisms and address issues of concern that could impact our patients, clients, staff, and students. Methods: The OSU-CVM ASWG collects samples from >100 surfaces within the companion animal, farm animal, and equine sections of our hospital each month. Sampling has been continuous since January 2018. Samples are collected from both human–animal contact and human-only contact surfaces using Swiffer electrostatic cloths. These samples are cultured for recovery of Salmonella spp, extended-spectrum cephalosporin-resistant Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae (CPE), and methicillin-resistant Staphylococcus spp. Results: The recovery of these antibiotic resistant target organisms is low in the environment of our hospital. Recovery from human-only contact surfaces (19.8%) is very similar to recovery from human–animal contact surfaces (25.5%). We commonly recover Enterobacteriaceae (E.coli, Klebsiella spp, and Enterobacter spp) that are resistant to extended-spectrum cephalosporins (496 of 2,016; 24.6%) from the VMC environment. These antibiotic-resistant indicator bacteria are expected in a veterinary hospital setting where use the of β-lactam drugs is common. Recovery of both Salmonella spp and CPE has remained very low in our hospital environment over the past 19 months: 16 of 2,016 (0.7%) for Salmonella and 15 of 2,016 (0.8%) for CPE. Discussion: The active environmental surveillance component of our antimicrobial stewardship program has allowed us to reduce the threat of nosocomial infections within our hospital and address environmental contamination issues before they become a problem. Our consistently low recovery of resistant organisms indicates the effectiveness of our existing cleaning and disinfection protocols and biosecurity measures. Due to the nature of our patient population, we do expect to find resistant organisms in the patient-contact areas of the hospital environment. However, our similar rates of resistant organisms from human-only surfaces (eg, computer keyboards, door handles, telephones, and Cubex machines) indicates a need to improve our hand hygiene practices. These data are now supporting the implementation of a new hand hygiene campaign in our veterinary hospital.Funding: NoneDisclosures: None


Sign in / Sign up

Export Citation Format

Share Document