Evidence map›Paper›PMID 33536439›Full record

ArticleNature communications2021

High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming.

Guangan Hu, Yang Su, Byong Ha Kang, Zhongqi Fan, Ting Dong, Douglas R Brown, Jaime Cheah, Karl Dane Wittrup, Jianzhu Chen

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.

  1. Pooled it
  2. Article
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  5. Article
  6. Review
  7. Article
  8. TIM-3, a potential target for sepsis therapy.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026
    Review
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  19. Article
  20. Nutrients · 2025
    Article

14 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

9 authors at 2 institutions in 1 country.

Guangan HuKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. gahu@mit.edu.ORCID http://orcid.org/0000-0003-1828-0509
Yang SuKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Byong Ha KangKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-1637-2082
Zhongqi FanKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Ting DongKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Douglas R BrownKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Jaime CheahKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Karl Dane WittrupKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0003-2398-5896
Jianzhu ChenKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. jchen@mit.edu.ORCID http://orcid.org/0000-0002-5687-6154
Massachusetts Institute of Technology · USIIT@MIT · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Mucins and immune cell interactions in ovarian cancer pathogenesis & progressionR35CA197605 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CRAMER, DANIEL WILLIAM · 2016 to 2022
$6.9M
Therapeutic modulation of the phagocytosis axis as a novel glioblastoma immunotherapyR01NS104315 · NINDS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KIM, BETTY · 2018 to 2022
$1.7M
NCI NIH HHS P30 CA014051NCI NIH HHS R35 CA197605NINDS NIH HHS R01 NS104315
6 · The paper itself

Abstract

Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like macrophages toward M2-like state and another ~20 for the reverse repolarization. Transcriptional analyses of macrophages treated with 34 non-redundant compounds identify both shared and unique targets and pathways through which the tested compounds modulate macrophage activation. One M1-activating compound, thiostrepton, is able to reprogram tumor-associated macrophages toward M1-like state in mice, and exhibit potent anti-tumor activity. Our compound-screening results thus help to provide a valuable resource not only for studying the macrophage biology but also for developing therapeutics through modulating macrophage activation.

Indexed as

AnimalsAnti-Inflammatory AgentsBiological ProductsCell Line, TumorCells, CulturedGene ExpressionGene OntologyHigh-Throughput Screening AssaysHumansMacrophage ActivationMacrophagesMiceMice, Inbred C57BLNeoplasms, ExperimentalPhenotypeThiostreptonAnti-Inflammatory AgentsBiological ProductsThiostrepton

Identifiers

PMID33536439
PMCPMC7858590
OpenAlexW3128859299

What OpenQuestion holds

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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.