Evidence map›Paper›PMID 25294906›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

MHC class I loss is a frequent mechanism of immune escape in papillary thyroid cancer that is reversed by interferon and selumetinib treatment in vitro.

Trevor E Angell, Melissa G Lechner, Julie K Jang, Jonathan S LoPresti, Alan L Epstein

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 3 pooled it
6.0field-weighted citation impact, top 3% 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

98 citing papers in PubMed, 3 syntheses or guidelines pooled it, 151 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

38 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Trevor E AngellDivision of Endocrinology and Diabetes, Keck Medical Center, University of Southern California, Los Angeles, California. Department of Pathology, Keck Medical Center, University of Southern California, Los Angeles, California. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Melissa G LechnerDepartment of Pathology, Keck Medical Center, University of Southern California, Los Angeles, California. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Julie K JangDepartment of Pathology, Keck Medical Center, University of Southern California, Los Angeles, California.
Jonathan S LoPrestiDivision of Endocrinology and Diabetes, Keck Medical Center, University of Southern California, Los Angeles, California.
Alan L EpsteinDepartment of Pathology, Keck Medical Center, University of Southern California, Los Angeles, California. aepstein@usc.edu.
University of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Training in Genetic, Molecular and Cellular BiologyT32GM067587 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI STALLCUP, MICHAEL R · 2003 to 2012
$1.8M
Southern California Clinical and Translational Science InstituteTL1TR000132 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2014
$491k
NCATS NIH HHS TL1 TR000132NCATS NIH HHS TL1TR000132NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089NIGMS NIH HHS 3T32GM067587-07S1NIGMS NIH HHS T32 GM067587
6 · The paper itself

Abstract

purposeTo evaluate MHC class I expression on papillary thyroid cancer (PTC) and analyze changes in MHC expression and associated immune activation with current and experimental treatments for thyroid cancer using in vitro PTC cell lines. EXPERIMENTAL

designMHC class I expression and assessment of tumor-infiltrating leukocyte populations were evaluated by immunohistochemistry. PTC cell lines were analyzed for HLA-ABC expression by flow cytometry following tyrosine kinase inhibitor, IFNα or IFNγ, or radiation treatment. Functional changes in antigenicity were assessed by coculture of allogeneic donor peripheral blood leukocytes (PBL) with pretreated or untreated PTC cell lines and measurement of T-cell activation and cytokine production.

resultsBoth MHC class I and β2-microglobulin expression was reduced or absent in 76% of PTC specimens and was associated with reduced tumor-infiltrating immune cells, including effector (CD3(+), CD8(+), CD16(+)) and suppressor (FoxP3(+)) populations. Treatment of PTC cell lines with the MEK1/2 inhibitor selumetinib or IFN increased HLA-ABC expression. This phenotypic change was associated with increased T-cell activation (%CD25(+) of CD3(+)) and IL2 production by PBL cocultured with treated PTC cell lines. Additive effects were seen with combination selumetinib and IFN treatment.

conclusionsMHC class I expression loss is frequent in human PTC specimens and represents a significant mechanism of immune escape. Increased antigenicity following selumetinib and IFN treatment warrants further study for immunotherapy of progressive PTC.

Indexed as

AdultAgedBenzimidazolesBiomarkersCarcinomaCarcinoma, PapillaryCell Line, TumorDrug SynergismFemaleGene ExpressionGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansImmunohistochemistryInterferonsLymphocytes, Tumor-InfiltratingAZD 6244BenzimidazolesBiomarkersHistocompatibility Antigens Class IInterferonsProtein Kinase InhibitorsProto-Oncogene Proteins B-raf

Identifiers

PMID25294906
PMCPMC4252612
OpenAlexW2136498843

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.