Evidence map›Paper›PMID 29733528›Full record

ArticleCancer medicine2018

Anti-PD-1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases.

Pooja Dhupkar, Nancy Gordon, John Stewart, Eugenie S Kleinerman

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.

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

62 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

4 authors at 1 institution in 1 country.

Pooja DhupkarDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-9290-7069
Nancy GordonDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
John StewartDivision of Pathology/Lab Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Eugenie S KleinermanDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
The University of Texas MD Anderson Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteosarcoma (OS) pulmonary metastasis translates into poor patient survival. The implication of PD-1-PD-L1 pathway in the context of NK cells and/or macrophages in OS is unknown. We investigated the effect of anti-PD-1 in OS lung metastasis and the role of NK cells and/or macrophages in anti-PD-1 responses. A human LM7 OS mouse model was used. Immunohistochemistry for tissues (PD-L1, caspase-3, Ki-67, NK cells, macrophages), and Western blotting for OS lung tumors (p-Stat3, p-Erk1/2) was performed. NK and macrophages were assessed using flow cytometry. NK cell and macrophage depletion were conducted using anti-asialo GM1 and clodrosome, respectively. PD-L1 expression was observed in human OS cells and OS patient lung metastases. Anti-PD1 antibody led to a significant decrease in the number of OS lung metastases, enhanced tumor apoptosis, decreased tumor cell proliferation, and p-STAT-3/p-Erk1/2 signaling blockade in OS lung tumors. NK cells and macrophages in OS lung tumors expressed PD-1 and anti-PD1 increased NK cell and macrophage tumor infiltration. Increased numbers of antitumor M1 macrophages and decreased pro-inflammatory M2 macrophages were seen. NK depletion did not affect therapeutic effect of anti-PD-1, suggesting that NK cells were not directly involved. However, macrophage depletion significantly compromised anti-PD1 efficacy, confirming their role in efficacy of anti-PD-1 against OS lung metastasis. Our findings suggest that OS lung metastases regression by anti-PD1 can be attributed to activated tumor M1 macrophages and reduced M2 macrophages. Owing to the co-relation of M1 macrophages with OS patient outcome, we provide a novel mechanism of PD-1 blockade and a basis for future clinical trials for anti-PD-1 antibodies in OS.

Indexed as

PhenotypeAnimalsAntineoplastic Agents, ImmunologicalApoptosisB7-H1 AntigenBiomarkers, TumorCell Line, TumorCell ProliferationDisease Models, AnimalHumansImmunomodulationKiller Cells, NaturalLung NeoplasmsMacrophagesMiceOsteosarcomaAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD274 protein, humanImmunotherapylung metastasismacrophagesosteosarcomaprogrammed death ligand-1

Identifiers

PMID29733528
PMCPMC6010882
OpenAlexW2800405451

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.