Evidence map›Paper›PMID 30626487›Full record

ArticleGynecologic oncology2019

MUC16 suppresses human and murine innate immune responses.

Mildred Felder, Arvinder Kapur, Alexander L Rakhmilevich, Xiaoyi Qu, Paul M Sondel, Stephen D Gillies, Joseph Connor, Manish S Patankar

Open access · hybridAbstract read
In one paragraph

Article in Gynecologic oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. [MUC16: The Novel Target for Tumor Therapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022
    Review
  14. Article
  15. Article
  16. MUC16 promotes EOC proliferation by regulating GLUT1 expression.Journal of cellular and molecular medicine · 2021
    Article
  17. Article
  18. Article
  19. Article
  20. Immunology and ovarian cancers.Journal of the Chinese Medical Association : JCMA · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Mildred FelderDepartment of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA.
Arvinder KapurDepartment of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA.
Alexander L RakhmilevichDepartment of Human Oncology, University of Wisconsin, Madison, WI, USA.
Xiaoyi QuDepartment of Human Oncology, University of Wisconsin, Madison, WI, USA.
Paul M SondelDepartments of Pediatrics and Human Oncology, University of Wisconsin, Madison, WI, USA.
Stephen D GilliesProvenance Biopharmaceuticals, Carlisle, MA, USA.
Joseph ConnorDepartment of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53792, USA. Electronic address: jconnor@uwhealth.org.
Manish S PatankarDepartment of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA. Electronic address: patankar@wisc.edu.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
T-Cell Independent Antitumor Mechanisms of CD40 LigationR01CA087025 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SONDEL, PAUL M · 2002 to 2012
$2.4M
Ovarian cancer diagnosis by monitoring immune cell bound MUC16 (CA125)R21CA143616 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI PATANKAR, MANISH S · 2010 to 2011
$350k
Improving Ovarian Cancer Treatment by Targeting a Novel Epitope of MUC16R41CA132520 · NCI · NEOCLONE BIOTECHNOLOGY INTERNATIONAL · PI CONNOR, JOSEPH P, KRAVITZ, RACHEL HANNAH · 2009 to 2009
$191k
NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA087025NCI NIH HHS R21 CA143616NCI NIH HHS R41 CA132520
6 · The paper itself

Abstract

objectiveMUC16, the mucin that contains the CA125 epitopes, suppresses the cytolytic responses of human NK cells and inhibits the efficacy of therapeutic antibodies. Here, we provide further evidence of the regulatory role of MUC16 on human and murine NK cells and macrophages.

methodsTarget cell cytolysis and doublet formation assays were performed to assess effects of MUC16 on human NK cells. The effect of MUC16 on ovarian tumor growth was determined in a mouse model by monitoring survival and ascites formation. Innate immune cells from spleens and peritoneal cavities of mice were isolated and stimulated in vitro with anti-CD40 antibody, lipopolysaccharide and IFN-γ and their ability to cytolyse MUC16 expressing and non-expressing cells was determined.

resultsWe confirm that MUC16 inhibits cytolysis by human NK cells as well as the formation of NK-tumor conjugates. Mice implanted with MUC16-knockdown OVCAR-3 show >2-fold increase in survival compared to controls. Murine NK cells and macrophages are more efficient at lysing MUC16-knockdown cells. In vitro cytotoxicity assays with NK cells and macrophages isolated from mice stimulated with anti-CD40 antibody showed 2-3-fold increased activity against the MUC16-knockdown cells as compared to matching target cells expressing this mucin. Finally, knockdown of MUC16 increased the susceptibility of cancer cells to ADCC by murine splenocytes.

conclusionsFor the first time, we demonstrate the immunoregulatory effects of MUC16 on murine NK cells and macrophages. Our study implies that the immunoregulatory role of MUC16 on murine NK cells and macrophages should be considered when examining the biology of MUC16 in mouse models.

Indexed as

AnimalsCA-125 AntigenCell Line, TumorFemaleHumansImmunity, InnateKiller Cells, NaturalMacrophagesMelanoma, ExperimentalMembrane ProteinsMiceMice, Inbred C57BLMice, SCIDOvarian NeoplasmsCA-125 AntigenMembrane ProteinsMUC16 protein, humanMUC16 protein, mouseAntibody-mediated cytotoxicityCA125Immune evasionImmunesuppressionMUC16NK cellsOvarian cancer

Identifiers

PMID30626487
PMCPMC8327469
OpenAlexW2907037836

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.