Evidence map›Paper›PMID 42588697›Full record

ArticleCancers2026

DNA Methyltransferase Inhibitors, Decitabine and Guadecitabine Overcome Immune-Checkpoint Blockade Resistance and Achieve Tumor Regression in the E0771 and 4T1 Murine Models of Triple-Negative Breast Cancer.

S Jennifer Wang, Carolyn Haynes, Laura Graham, Akhila Kunuthuru, Gina Tuzzolo, Anaya Surve, Madison Isbell, Jian He, Rebecca K Martin, Harry Bear

Abstract read
In one paragraph

Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

S Jennifer WangSchool of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0001-5719-1037
Carolyn HaynesDepartment of Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA.
Laura GrahamDepartment of Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA.
Akhila KunuthuruSchool of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Gina TuzzoloSchool of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Anaya SurveSchool of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Madison IsbellFlow Cytometry Shared Resource, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Jian HeBiostatistics Shared Resource, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-3796-4623
Rebecca K MartinFlow Cytometry Shared Resource, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0001-9948-5463
Harry BearDivision of Surgical Oncology, Department of Surgery and the Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-7632-9019

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI PAUL M FAWCETT · 1985 to 2026
$51.0M
NCI NIH HHS P30 CA016059
6 · The paper itself

Abstract

backgroundImmune-checkpoint blockade (ICB) is a recent addition to the treatment options for breast cancer, especially the triple-negative (TNBC) subset. Inhibiting immunosuppressive factors in the tumor microenvironment (TME) and preventing or reversing T cell exhaustion may increase the likelihood of a response to ICB. We have shown that decitabine and guadecitabine, DNA methyltransferase inhibitors (DNMTi), prevent the systemic and TME accumulation of myeloid-derived suppressor cells (MDSCs), which are immunosuppressive.

resultsHere, we show that adding DNMTi to the neoadjuvant + adjuvant ICB-based treatment of ICB-resistant 4T1 and E0771 murine tumors in Balb/C and C57Bl/6 mice, respectively, effectively reduced the tumor burden, with 52% of 4T1 tumors completely regressing across several studies. DNMTi-based therapy overcame ICB resistance (ICBR) in a selected subline of E0771, and treated tumors showed a reduction in MDSCs. We also show that, in E0771, DNMTi can overcome ICBR to multiple checkpoint inhibitors, and in 4T1, it can modulate anti-tumor immunity by enhancing central memory T cell (Tcm) formation and reducing T cell exhaustion.

conclusionThese pre-clinical findings support the further investigation of incorporating DNMTi as a new immunotherapy modality for TNBC.

Indexed as

4T1decitabineDNA methyltransferase inhibitorE0771guadecitabineimmunotherapytriple-negative breast cancer

Identifiers

PMID42588697
PMCPMC13464779

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.