Evidence map›Paper›PMID 42010915›Full record

ArticleJournal of immunology research2026

High-Throughput Heterospheroid-Based Screening Identifies Drugs That Reprogram Tumor-Associated Macrophages.

Hiroyuki Tsuchiya, Takehiko Hanaki, Mayu Obora, Jun Yoshida, Mikiya Kishino, Yoshiyuki Fujiwara, Daisuke Nanba

Abstract read
In one paragraph

Article in Journal of immunology research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

7 authors.

Hiroyuki TsuchiyaDivision of Regenerative Medicine and Therapeutics, Department of Genomic Medicine and Regenerative Therapy, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, tottori-u.ac.jp.ORCID https://orcid.org/0000-0002-2144-8272
Takehiko HanakiDivision of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, tottori-u.ac.jp.ORCID https://orcid.org/0000-0002-4008-0207
Mayu OboraDivision of Regenerative Medicine and Therapeutics, Department of Genomic Medicine and Regenerative Therapy, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, tottori-u.ac.jp.
Jun YoshidaDivision of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, tottori-u.ac.jp.
Mikiya KishinoDivision of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, tottori-u.ac.jp.
Yoshiyuki FujiwaraDivision of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, tottori-u.ac.jp.
Daisuke NanbaDivision of Regenerative Medicine and Therapeutics, Department of Genomic Medicine and Regenerative Therapy, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, tottori-u.ac.jp.ORCID https://orcid.org/0000-0002-9765-9113

Funding

Japan Society for the Promotion of Science 23K07437
6 · The paper itself

Abstract

The tumor microenvironment (TME) provides a niche for immune evasion and immunotherapy resistance, in part, by recruiting pro-tumor M2-like macrophages. In the present study, using heterospheroids consisting of cancer cells and macrophages, we identified TAM activators, which are compounds that reprogram M2-like tumor-associated macrophages (TAMs) toward the antitumor M1-like phenotype. THP-1- or human peripheral monocyte-derived macrophages were co-cultured with liver cancer (LC) cells in an ultra-low attachment dish to generate heterospheroids. Cell surface marker expression and macrophage infiltration into the heterospheroids were assessed by flow cytometry and fluorescence microscopy, respectively. Lipopolysaccharide (LPS) and interferon-γ (IFNγ)-induced M1 marker expression was observed on the macrophages in the homospheroids; however, this induction was suppressed in heterospheroids. Microscopic imaging revealed that macrophage infiltration into the heterospheroids was decreased in the presence of LPS and IFNγ, which prompted us to develop a high-content imaging screen. We identified two compounds [alprostadil (prostaglandin E1) and HX531] with TAM-activating activity. RNA-seq analysis revealed that HX531 modulated the immune and IFN response in cancer cells and cell division in macrophages. Moreover, alprostadil promoted the M1-like polarization of TAMs, increased tumor-infiltrating CD8

Indexed as

Antineoplastic AgentsLiver NeoplasmsTumor-Associated MacrophagesAnimalsCell Line, TumorCoculture TechniquesHigh-Throughput Screening AssaysHumansInterferon-gammaMacrophage ActivationMiceTumor MicroenvironmentAntineoplastic AgentsInterferon-gammaheterospheroidhigh-content imaging analysismacrophage reprogrammingscreeningtumor-associated macrophage

Identifiers

PMID42010915
PMCPMC13581048

What Socratic 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 Socratic graph.