Evidence map›Paper›PMID 40756608›Full record

ArticleImmunotherapy advances2025

SMAC mimetics induce human macrophages to phagocytose live cancer cells.

Samantha Y Liu, Max P M Hulsman, Philipp Leyendecker, Eugena Chang, Katherine A Donovan, Fabian Strobel, James Dougan, Eric S Fischer, Michael Dougan, Stephanie K Dougan and 1 more

Abstract read
In one paragraph

Article in Immunotherapy advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Second Mitochondrial Activator of Caspases Mimetics Accelerate Progression of Locally Advanced Head and Neck Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Samantha Y LiuDana-Farber Cancer Institute, Department of Cancer Immunology and Virology, Boston, Massachusetts, US.
Max P M HulsmanDana-Farber Cancer Institute, Department of Cancer Immunology and Virology, Boston, Massachusetts, US.
Philipp LeyendeckerDana-Farber Cancer Institute, Department of Cancer Immunology and Virology, Boston, Massachusetts, US.
Eugena ChangDana-Farber Cancer Institute, Department of Cancer Immunology and Virology, Boston, Massachusetts, US.
Katherine A DonovanDana-Farber Cancer Institute, Department of Cancer Biology, Boston, Massachusetts, US.
Fabian StrobelDana-Farber Cancer Institute, Department of Cancer Immunology and Virology, Boston, Massachusetts, US.
James DouganBrookline High School, Boston, Massachusetts, US.
Eric S FischerDana-Farber Cancer Institute, Department of Cancer Biology, Boston, Massachusetts, US.
Michael DouganMassachussets General Hospital, Department of Medicine, Division of Gastroenterology, Boston, Massachusetts, US.
Stephanie K DouganDana-Farber Cancer Institute, Department of Cancer Immunology and Virology, Boston, Massachusetts, US.ORCID https://orcid.org/0000-0002-2263-363X
Li QiangDana-Farber Cancer Institute, Department of Cancer Immunology and Virology, Boston, Massachusetts, US.ORCID https://orcid.org/0000-0002-2354-177X

Funding

Stromal modulation of pancreatic cancer malignant cell state and therapeutic sensitivityU01CA274276 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre, Stephanie Dougan · 2022 to 2026
$5.1M
Molecular Pathways Regulating Tissue-resident Memory T cells in the GutR01AI169188 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Michael Lawrence Dougan · 2022 to 2026
$3.0M
CDK4/6 inhibition during CD8 T cell priming potentiates memory formation in mice and humansR01AI158488 · NIAID · DANA-FARBER CANCER INST · PI DOUGAN, STEPHANIE · 2021 to 2025
$2.2M
Development of a generalizable chemo-proteomics screening platform for small molecule degraders applied to HDACsR01CA262188 · NCI · DANA-FARBER CANCER INST · PI FISCHER, ERIC SEBASTIAN · 2022 to 2025
$1.8M
NCI NIH HHS R01 CA262188NCI NIH HHS U01 CA274276NIAID NIH HHS R01 AI158488NIAID NIH HHS R01 AI169188
6 · The paper itself

Abstract

Macrophages engulf apoptotic bodies and cellular debris as part of homeostasis, but they can also phagocytose live cells, such as aged red blood cells. Pharmacologic reprogramming with the SMAC mimetic LCL161 in combination with T-cell-derived cytokines can induce macrophages to phagocytose live cancer cells in mouse models. Here we extend these findings to encompass a wide range of monovalent and bivalent SMAC mimetic compounds, demonstrating that live cell phagocytosis is a class effect of these agents. We demonstrate robust phagocytosis of live pancreatic and breast cancer cells by primary human macrophages across a range of healthy donors. Unlike mouse macrophages, where a combination of SMAC mimetics with lymphotoxin enhanced phagocytosis, human macrophages were more efficiently polarized to phagocytose live cells by the combination of SMAC mimetics and IFNg. We profiled phagocytic macrophages by transcriptional and proteomic methodologies, uncovering a positive feedback loop of autocrine TNFa production.

Indexed as

IAP antagonistLCL-161LCL161macrophageNF-kBphagocytosisSMAC mimetic

Identifiers

PMID40756608
PMCPMC12314603

What OpenQuestion holds

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Registered trials

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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.