Evidence map›Paper›PMID 42651843›Full record

ArticleCurrent issues in molecular biology2026

Tumor-Intrinsic DNA Damage Signaling Is Associated with MHC-I Expression and CD8 Cytotoxic T-Cell Engagement in Triple-Negative Breast Cancer.

Zinab O Doha, Ezzat AbuAzzah, Hakeemah H Al-Nakhle

Abstract read
In one paragraph

Article in Current issues in molecular biology, 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

3 authors.

Zinab O DohaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.ORCID 0000-0003-2952-9840
Ezzat AbuAzzahDepartment of Radiologic Technology, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.ORCID 0000-0002-5806-3130
Hakeemah H Al-NakhleDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.ORCID 0000-0002-5311-7072

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is characterized by marked immune microenvironment heterogeneity and variable chemotherapy response, yet the epithelial transcriptional programs governing cytotoxic immune activation remain poorly understood. We performed an exploratory, integrative analysis using single-cell RNA sequencing of 31,962 cells from eight TNBC patients operationally stratified into Good and Bad Prognosis groups based on pathological lymphoid infiltration, a discovery grouping subsequently validated against pathological complete response (pCR) in three independent bulk RNA-seq cohorts. This analysis identified four epithelial transcriptional states. The G5 DNA damage subpopulation-predominantly restricted to Good Prognosis tumors (29.2% vs. 0%)-and the G4 Metabolism subpopulation-2.4-fold enriched in Bad Prognosis-were the primary prognostic signatures. Machine learning validation using nested leave-one-cohort-out (LOCO) cross-validation across 614 samples demonstrated that G4 + G5 raw genes with random forest yielded the largest observed mean AUC of 0.653, though these results are exploratory and do not establish a validated clinical classifier. CellChat ligand-receptor interaction analysis revealed that G5 DNA-damage epithelial cells are the dominant immune activators in Good Prognosis TNBC, predominantly engaging CD8 cytotoxic T cells through MHC-I antigen presentation via HLA-A/B/C/E/F → CD8A/CD8B interactions, the highest-probability signaling pathway identified. Spatial transcriptomics independently validated significantly higher DNA damage and CD8 T-cell scores in Good Prognosis tissue. Together, these exploratory findings suggest a framework in which tumor-intrinsic DNA damage signaling is associated with MHC-I antigen presentation upregulation and CD8 cytotoxic T-cell engagement, supporting further investigation of this axis and its potential implications for combining DNA-damaging chemotherapy with immune checkpoint blockade in TNBC.

Indexed as

CD8 cytotoxic T cellsDNA damage responseligand–receptor interactionsmachine learningMHC-I antigen presentationprognosissingle-cell RNA sequencingspatial transcriptomicstriple-negative breast cancertumor microenvironment

Identifiers

PMID42651843
PMCPMC13510773

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.