Evidence map›Paper›PMID 28288138›Full record

ArticleOncogene2017

MUC1-C integrates PD-L1 induction with repression of immune effectors in non-small-cell lung cancer.

A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe and 3 more

Open access · greenAbstract read
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
5.5field-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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
  2. Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  3. Article
  4. Article
  5. Review
  6. Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026
    Review
  7. Do Metastatic Cells Arise from PD-L1International journal of molecular sciences · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
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28 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

13 authors at 2 institutions in 1 country.

A BouillezMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
H RajabiMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
C JinMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M SamurMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
A TagdeMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M AlamMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M HirakiMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
T MaedaMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
X HuMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
D AdeegbeMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
S KharbandaMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
K-K WongMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
D KufeMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Harvard University · USDana-Farber Cancer Institute · US

Funding

Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0M
Targeting the MUC1-C Oncoprotein in Triple-Negative Breast CancerR01CA097098 · NCI · DANA-FARBER CANCER INSTITUTE · PI DONALD W. KUFE · 2002 to 2026
$8.8M
MUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung CancerR01CA166480 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W., WONG, KWOK KIN · 2012 to 2021
$6.3M
Immunotherapeutic Approaches Targeting the MUC1-C Oncoprotein in Triple-Negative Breast CancerR21CA216553 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W. · 2017 to 2018
$377k
NCI NIH HHS P50 CA100707NCI NIH HHS R01 CA097098NCI NIH HHS R01 CA166480NCI NIH HHS R21 CA216553
6 · The paper itself

Abstract

Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65→︀ZEB1 pathway and confers a poor prognosis. The present studies demonstrate that MUC1-C activates PD-L1 expression in NSCLC cells. We show that MUC1-C increases NF-κB p65 occupancy on the CD274/PD-L1 promoter and thereby drives CD274 transcription. Moreover, we demonstrate that MUC1-C-induced activation of NF-κB→︀ZEB1 signaling represses the TLR9 (toll-like receptor 9), IFNG, MCP-1 (monocyte chemoattractant protein-1) and GM-CSF genes, and that this signature is associated with decreases in overall survival. In concert with these results, targeting MUC1-C in NSCLC tumors suppresses PD-L1 and induces these effectors of innate and adaptive immunity. These findings support a previously unrecognized central role for MUC1-C in integrating PD-L1 activation with suppression of immune effectors and poor clinical outcome.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsA549 CellsAnimalsB7-H1 AntigenCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunity, CellularMiceMice, NudeMucin-1Signal TransductionTumor EscapeB7-H1 AntigenCD274 protein, humanMUC1 protein, humanMucin-1

Identifiers

PMID28288138
PMCPMC5509481
OpenAlexW2596245384

What OpenQuestion holds

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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.