ArticleJournal for immunotherapy of cancer2026
Inhibition of histone demethylase LSD1 suppresses CD47 expression and enhances efficacy of CD47 blockade in breast cancer.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundCD47 functions as a "don't eat me" checkpoint, inhibiting macrophage-mediated phagocytosis in triple-negative breast cancer (TNBC). While anti-CD47 therapies can restore immune surveillance, their efficacy in TNBC is often limited by immune evasion and drug development challenges.
methodsWe investigated the crosstalk between the histone demethylase lysine-specific demethylase 1 (LSD1) and CD47 signaling in TNBC using
resultsIn TNBC tumors, CD47 expression is positively correlated with elevated LSD1 levels, which are associated with increased infiltration of M2 macrophages and a concomitant decrease in M1 macrophages and CD8+T cells. Inhibition of LSD1 led to downregulation of CD47 by suppressing the expression and activity of its key transcriptional regulators, NF-κB (p65) and STAT3, through distinct mechanisms. Loss of LSD1 reduced p65 transcription, which was linked to an accumulation of the repressive histone mark H3K9me2 at the p65 promoter. Conversely, LSD1 inhibition promoted polyubiquitination and subsequent destabilization of STAT3. LSD1 inhibition also enhanced phagocytosis and promoted M1 polarization of macrophages. CD47 downregulation induced the production of interferon-γ and Th1-type chemokines in TNBC cells, facilitating increased tumor infiltration of CD8+T cells. Furthermore, combining LSD1 inhibition with anti-CD47 therapy significantly improved antitumor efficacy compared with monotherapy in syngeneic tumor models, without inducing significant toxicity. This combination therapy also promoted a shift in macrophage polarization toward the M1 phenotype, further enhancing CD8+T cell infiltration within tumors. Depletion of CD8+T cells significantly diminished the antitumor efficacy of the combination therapy.
conclusionTargeting LSD1 enhances the efficacy of anti-CD47 therapy by overcoming immune evasion, offering a promising strategy to improve immunotherapy outcomes in TNBC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.