Evidence map›Paper›PMID 40883548›Full record

ArticleAnnals of biomedical engineering2025

Locally Reprogramming Tumor-Associated Macrophages with Cytokine-Loaded Injectable Cryogels for Breast Cancer.

Sydney R Henriques, Evan B Glass, Kristen L Hoek, Ori Z Chalom, Abigail E Manning, Sohini Roy, Diana K Graves, Sarah M Goldstein, Benjamin C Hacker, Renjie Jin and 7 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of biomedical engineering, 2025. 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 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. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Sydney R Henriques *Department of Biomedical Engineering, Vanderbilt University, Nashville, USA.
Evan B Glass *Department of Biomedical Engineering, Vanderbilt University, Nashville, USA.
Kristen L HoekDepartment of Pharmacology, Vanderbilt University, Nashville, USA.
Ori Z ChalomDepartment of Biomedical Engineering, Vanderbilt University, Nashville, USA.
Abigail E ManningDepartment of Biomedical Engineering, Vanderbilt University, Nashville, USA.
Sohini RoyDepartment of Otolaryngology, Vanderbilt University Medical Cente, Nashville, USA.
Diana K GravesDepartment of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, USA.
Sarah M GoldsteinDepartment of Biomedical Engineering, Vanderbilt University, Nashville, USA.
Benjamin C HackerDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, USA.
Renjie JinDepartment of Pharmacology, Vanderbilt University, Nashville, USA.
Marjan RafatDepartment of Biomedical Engineering, Vanderbilt University, Nashville, USA.
Paula J HurleyDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Laura C KennedyDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Young J KimDepartment of Otolaryngology, Vanderbilt University Medical Cente, Nashville, USA.
Andrew J WilsonVanderbilt Ingram Cancer Center, Nashville, USA.
Fiona E YullDepartment of Pharmacology, Vanderbilt University, Nashville, USA.
Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, USA. todd.d.giorgio@vanderbilt.edu.ORCID http://orcid.org/0000-0002-9557-1425

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2002 to 2026
$29.9M
Macrophage-based ovarian cancer immunotherapyR01CA214043 · NCI · VANDERBILT UNIVERSITY · PI GIORGIO, TODD D, KHABELE, DINEO · 2017 to 2021
$1.9M
NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA214043NIDDK NIH HHS P30 DK058404NIH HHS CA214043U.S. Department of Defense BC180963
6 · The paper itself

Abstract

purposeTumor-associated macrophages (TAMs) are the most abundant immune cells in primary solid tumors, including breast cancer, and typically exhibit an M2-like, immunosuppressive phenotype that promotes tumor growth. Given that TAMs can be repolarized through cytokine signaling, we propose a localized cytokine delivery depot using an injectable alginate cryogel to reprogram TAMs and create an inflammatory, anti-tumor TME.

methodsThe cryogels were fabricated using cryogelation to generate a macroporous structure, followed by ionic crosslinking to enhance mechanical integrity while preserving pore size distribution. In vitro studies were conducted using bone marrow-derived macrophages, tumor-associated macrophages, and tumor explants. In vivo studies were conducted by orthotopically implanting breast tumors in the fat pads of FVB mice. Cell makeup and tissue composition were analyzed using qRT-PCR, flow cytometry, and Luminex panels. Statistical significance was determined using ANOVA and t-tests.

resultsIn vitro, cryogels released chemokines and cytokines, attracted M2 macrophages, and repolarized them toward M1-like activities. In vivo, cryogel treatment increased the presence of M1 macrophages relative to M2 macrophages in both the primary tumor and lungs, reduced primary tumor growth, and decreased T-cell exhaustion.

conclusionsA localized, injectable cryogel depot successfully induces an inflammatory TME, leading to reduced tumor burden and T-cell exhaustion while avoiding systemic toxicities associated with cytokine delivery.

Indexed as

Breast NeoplasmsCryogelsCytokinesTumor-Associated MacrophagesAnimalsCell Line, TumorFemaleHumansMiceCryogelsCytokinesBreast cancerCryogelsCytokinesImmunotherapyMacrophagesTumor microenvironment

Identifiers

PMID40883548
PMCPMC12575589

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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.