Evidence map›Paper›PMID 38893094›Full record

ArticleCancers2024

TWIST1 Drives Cytotoxic CD8+ T-Cell Exhaustion through Transcriptional Activation of

Xiaobin Yu, Jianming Xu

Abstract read
In one paragraph

Article in Cancers, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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  6. Article
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  13. CD8Frontiers in immunology · 2024
    Review
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

2 authors.

Xiaobin YuDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jianming XuDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Funding

NCOA6, A Novel Tumor Suppressor of Endometrial CancerR01CA193455 · NCI · BAYLOR COLLEGE OF MEDICINE · PI XU, JIANMING · 2016 to 2021
$1.9M
The function of TWIST1 acetylation in cell fate and tissue developmentR21DE033147 · NIDCR · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI FAKHOURI, WALID D., XU, JIANMING · 2023 to 2023
$449k
The primary role of low NCOA6 expression in the prostate cancer disparity among African American menR21CA267006 · NCI · BAYLOR COLLEGE OF MEDICINE · PI XU, JIANMING · 2022 to 2023
$408k
NCI NIH HHS R01 CA193455NCI NIH HHS R21 CA267006NIDCR NIH HHS R21 DE033147NIH HHS R01CA193455NIH HHS R21CA267006NIH HHS R21DE033147
6 · The paper itself

Abstract

In breast cancer, epithelial-mesenchymal transition (EMT) is positively associated with programmed death ligand 1 (PD-L1) expression and immune escape, and TWIST1 silences ERα expression and induces EMT and cancer metastasis. However, how TWIST1 regulates PD-L1 and immune evasion is unknown. This study analyzed TWIST1 and PD-L1 expression in breast cancers, investigated the mechanism for TWIST1 to regulate PD-L1 transcription, and assessed the effects of TWIST1 and PD-L1 in cancer cells on cytotoxic CD8+ T cells. Interestingly, TWIST1 expression is correlated with high-level PD-L1 expression in ERα-negative breast cancer cells. The overexpression and knockdown of TWIST1 robustly upregulate and downregulate PD-L1 expression, respectively. TWIST1 binds to the PD-L1 promoter and recruits the TIP60 acetyltransferase complex in a BRD8-dependent manner to transcriptionally activate PD-L1 expression, which significantly accelerates the exhaustion and death of the cytotoxic CD8+ T cells. Accordingly, knockdown of TWIST1 or BRD8 or inhibition of PD-L1 significantly enhances the tumor antigen-specific CD8+ T cells to suppress the growth of breast cancer cells. These results demonstrate that TWIST1 directly induces PD-L1 expression in ERα-negative breast cancer cells to promote immune evasion. Targeting TWIST1, BRD8, and/or PD-L1 in ERα-negative breast cancer cells with TWIST1 expression may sensitize CD8+ T-cell-mediated immunotherapy.

Indexed as

breast cancerEMTimmune-checkpoint-inhibitor therapyimmunosuppressionmetastasisPD-L1TWIST1

Identifiers

PMID38893094
PMCPMC11171171

What Socratic holds

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LicenceCC BY
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.