Evidence map›Paper›PMID 40858992›Full record

ArticleCommunications biology2025

Plasma exosomes from individuals with type 2 diabetes drive breast cancer aggression in patient-derived organoids.

Christina S Ennis, Michael Seen, Andrew Chen, Heejoo Kang, Adrian Ilinski, Kiana Mahdaviani, Naomi Y Ko, Stefano Monti, Gerald V Denis

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Christina S EnnisCancer Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Michael SeenCancer Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0009-0008-7823-1526
Andrew ChenDepartment of Medicine, Computational Biomedicine Section, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Heejoo KangCancer Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Adrian IlinskiSection of Hematology and Medical Oncology, Boston Medical Center, Boston, MA, USA.
Kiana MahdavianiSection of Hematology and Medical Oncology, Boston Medical Center, Boston, MA, USA.
Naomi Y KoSection of Hematology and Medical Oncology, Boston Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9689-9601
Stefano MontiDepartment of Medicine, Computational Biomedicine Section, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Gerald V DenisCancer Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA. gdenis@bu.edu.ORCID http://orcid.org/0000-0001-9886-0401

Funding

RESEARCH TRAINING IN IMMUNOLOGYT32AI007309 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GUMMULURU, SURYARAM · 1988 to 2024
$7.4M
Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancerR01CA222170 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI DENIS, GERALD V · 2018 to 2022
$3.1M
Uncoupling obesity from breast cancer in African American womenU01CA182898 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI DENIS, GERALD V, PALMER, JULIE R · 2013 to 2017
$3.1M
Multiscale analysis of metabolic inflammation as a driver of breast cancerU01CA243004 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI DENIS, GERALD V, EMILI, ANDREW · 2020 to 2024
$2.8M
NCI NIH HHS R01 CA222170NCI NIH HHS U01 CA182898NCI NIH HHS U01 CA243004NIAID NIH HHS T32 AI007309U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA222170U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA243004U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 5T32AI007309
6 · The paper itself

Abstract

Women with obesity-driven type 2 diabetes (T2D) face worse breast cancer outcomes, yet metabolic status does not fully inform current standards of care. We previously identified plasma exosomes as key drivers of tumor progression; however, their effect on immune cells within the tumor microenvironment (TME) remains unclear. Using a novel patient-derived organoid (PDO) system that preserves native tumor-infiltrating lymphocytes (TILs), we show that T2D plasma exosomes induce a 13.6-fold expansion of immunosuppressive TILs relative to nondiabetic controls. This immune dysfunction may promote micrometastatic survival and resistance to checkpoint blockade, a known issue in T2D cancer patients. Tumor-intrinsic analysis revealed a 1.5-fold increase in intratumoral heterogeneity and 2.3-fold upregulation of aggressive signaling networks. These findings reveal how T2D-associated metabolic dysregulation alters tumor-immune crosstalk through previously underappreciated exosomal signaling, impairing antitumor immunity and accelerating progression. Understanding these dynamics could inform tailored therapies for this high-risk, underserved patient population.

Indexed as

Breast NeoplasmsDiabetes Mellitus, Type 2ExosomesOrganoidsFemaleHumansLymphocytes, Tumor-InfiltratingTumor Microenvironment

Identifiers

PMID40858992
PMCPMC12381303

What Socratic 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 Socratic graph.