Evidence map›Paper›PMID 29296536›Full record

ArticleOncoimmunology

Crk adaptor protein promotes PD-L1 expression, EMT and immune evasion in a murine model of triple-negative breast cancer.

Sushil Kumar, Viralkumar Davra, Alison E Obr, Ke Geng, Teresa L Wood, Mariana S De Lorenzo, Raymond B Birge

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.6field-weighted citation impact, top 14% 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

34 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Immune evasion and resistance in breast cancer.American journal of cancer research · 2025
    Review
  5. Article
  6. Review
  7. M1 macrophages induce PD-L1Journal for immunotherapy of cancer · 2023
    Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. PD-1/PD-L1 axis in organ fibrosis.Frontiers in immunology · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Sushil KumarDepartment of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, USA.
Viralkumar DavraDepartment of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, USA.
Alison E ObrDepartment of Pharmacology, Physiology and Neuroscience, Rutgers University, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, USA.
Ke GengDepartment of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, USA.
Teresa L WoodDepartment of Pharmacology, Physiology and Neuroscience, Rutgers University, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, USA.
Mariana S De LorenzoDepartment of Cell Biology & Molecular Medicine Rutgers - New Jersey Medical School, Newark, NJ, USA
Raymond B BirgeDepartment of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, USA.
Rutgers, The State University of New Jersey · US

Funding

Pathways that regulate basal and metastatic phenotypes in triple negative breast cancersR01CA204312 · NCI · RBHS-NEW JERSEY MEDICAL SCHOOL · PI WOOD, TERESA L · 2017 to 2021
$2.7M
6 · The paper itself

Abstract

The tumor infiltration of immune cells in solid cancers can profoundly influence host antitumor responses. In recent years, immunotherapeutic regimens, that target immune checkpoints, demonstrated significant antitumor response by increasing intra-tumoral immune cell populations, including CD8+ effector T cells. However, administration of such immune checkpoint inhibitors is largely inefficacious in inducing immunogenicity and treating breast cancer. Currently, there is a great need to better understand cell autonomous mechanisms of immune evasion in breast cancer to identify upstream therapeutic targets that increase the efficacy of immunotherapy. Here we show that Crk, an SH2 and SH3 domain-containing adaptor protein implicated in focal adhesion signaling, cell migration, and invasion, and frequently up-regulated in human cancers, has an important role in regulating the tumor immune microenvironment. Using a murine 4T1 breast adenocarcinoma model of spontaneous metastasis in immune-competent BALB/C mice, we show that genetic ablation of Crk by CRISPR-Cas9 leads to enhanced anti-tumor immune cell populations, cytotoxic effector and immune surveillance cytokines in primary tumor. Pathologically, this leads to a significant reduction in tumor growth and lung metastasis. Mechanistically, Crk KO suppresses EMT and PD-L1 expression on tumor cells and acts additively with anti-PD1 therapy to suppress tumor growth and metastasis outcomes. Taken together, these data reveal a previously un-described function of Crk adaptor protein expression in tumor cells for cell autonomous regulation of tumor immune microenvironment.

Indexed as

breast cancerCrkmetastasisPD-L1tumor immunity

Identifiers

PMID29296536
PMCPMC5739568
OpenAlexW2750734739

What OpenQuestion holds

Textmetadata
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.