Evidence map›Paper›PMID 40977688›Full record

ArticleFrontiers in immunology2025

CRTC1 enhances PD-L1-mediated tumor immunosuppression in non-small cell lung cancer via the Notch1/Akt signaling pathway.

Xujun Feng, Yuan Shi, Fang Yuan, Yanxia Hu, Xiangdong Tang, Wei Zhang, Jiadi Gan, Longhua Sun, Lingling Cao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 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. Article
  2. Review
  3. Article
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

9 authors.

Xujun FengThe Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Yuan ShiSleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Fang YuanDepartment of Respiratory, The First Hospital of Jiujiang City, Jiujiang, Jiangxi, China.
Yanxia HuDepartment of Respiratory, The First Hospital of Jiujiang City, Jiujiang, Jiangxi, China.
Xiangdong TangSleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Wei ZhangThe Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Jiadi GanDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
Longhua SunThe Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Lingling CaoJiujiang City Key Laboratory of Cell Therapy, The First Hospital of Jiujiang City, Jiujiang, Jiangxi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: While programmed death-ligand 1 (PD-L1)-targeted immunotherapy represents an advancement in non-small cell lung cancer (NSCLC), patient outcomes remain suboptimal. Aberrant activation of the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB)-regulated transcription coactivator (CRTC) is linked to malignant proliferation and functionality in lung cancer cells. This study investigates the involvement of CRTC1 in tumor immunity. Methods: CRTC1 and Notch1 expression were regulated in A549 and NCI-H1299 NSCLC lines through plasmid-mediated overexpression/silencing to assess their effects on cell viability, apoptosis, migration, and invasion. CRTC1/Notch1-dysregulated Lewis lung carcinoma (LLC) cells were co-cultured with T cells to evaluate T cell activation and function. The efficacy of combined CRTC1 knockdown/overexpression and atezolizumab (anti-PD-L1) was tested in an LLC xenograft mouse model. Results: CRTC1 promoted cell viability, migration, and invasion while suppressing apoptosis across NSCLC models. In LLC cells, CRTC1 upregulated tumor cell PD-L1 expression, suppressed T cell-derived IFN-γ and IL-2 production, diminished endogenous CXCL10/11 secretion, and impaired T cell proliferation and cytotoxicity. Mechanistically, CRTC1 interacted with Notch1 to activate the Notch1/Akt pathway, stimulating PD-L1 upregulation, thereby facilitating tumor immunosuppression and growth. Notably, CRTC1 overexpression reversed the protective effects of atezolizumab on tumor growth. Combining CRTC1 knockdown with atezolizumab synergistically enhanced anti-tumor T cell immunity, achieving the most significant tumor regression in xenografts. Conclusion: These findings indicate that CRTC1 in tumor cells suppresses PD-L1-mediated anti-tumor immunity and promotes tumorigenesis via the Notch1/Akt signaling axis. Dual targeting of CRTC1 and PD-L1 demonstrates therapeutic synergy, suggesting CRTC1 pathway inhibition could optimize immunotherapy outcomes in NSCLC patients.

Indexed as

B7-H1 AntigenCarcinoma, Non-Small-Cell LungLung NeoplasmsProto-Oncogene Proteins c-aktReceptor, Notch1Transcription FactorsAnimalsAntibodies, Monoclonal, HumanizedApoptosisCell Line, TumorHumansMiceSignal TransductionXenograft Model Antitumor AssaysAntibodies, Monoclonal, HumanizedatezolizumabB7-H1 AntigenCD274 protein, humanCRTC1 protein, humanNOTCH1 protein, humanProto-Oncogene Proteins c-aktReceptor, Notch1Transcription FactorsCRTCimmunosuppressionimmunotherapynon-small cell lung cancerNotch/Akt signaling

Identifiers

PMID40977688
PMCPMC12446252

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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.