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Cited by 71Cancer Immunotherapy and BiomarkersLung Cancer Research StudiesFerroptosis and cancer prognosis

UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment

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Li, Yin, Jiang, Manling, Aye, Ling, Luo, Li, Zhang, Yong, Xu, Fengkai, Wei, Yongqi, Peng, Dan +6 more·2024·Nature Communications
DOI 10.1038/s41467-024-45340-wPMC PMC10853547
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Abstract

Abstract The complexity of the tumor microenvironment (TME) is a crucial factor in lung adenocarcinoma (LUAD) progression. To gain deeper insights into molecular mechanisms of LUAD, we perform an integrative single-cell RNA sequencing (scRNA-seq) data analysis of 377,574 cells from 117 LUAD patient samples. By linking scRNA-seq data with bulk gene expression data, we identify a cluster of prognostic-related UPP1 high tumor cells. These cells, primarily situated at the invasive front of tumors, display a stronger association with the immunosuppressive components in the TME. Our cytokine array analysis reveals that the upregulation of UPP1 in tumor cells leads to the increased release of various immunosuppressive cytokines, with TGF-β1 being particularly prominent. Furthermore, this UPP1 upregulation also elevates the expression of PD-L1 through the PI3K/AKT/mTOR pathway, which contributes to the suppression of CD8 + T cells. Cytometry by time-of-flight (CyTOF) analysis provides additional evidence of the role of UPP1 in shaping the immunosuppressive nature of the TME. Using patient-derived organoids (PDOs), we discover that UPP1 high tumors exhibit relatively increased sensitivity to Bosutinib and Dasatinib. Collectively, our study highlights the immunosuppressive role of UPP1 in LUAD, and these findings may provide insights into the molecular features of LUAD and facilitate the development of personalized treatment strategies.

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  • The CAF score and markers were significantly higher in the TBX3-overexpression group in scRNA-seq data.

    “the CAF score and markers were significantly higher in the TBX3-overexpression group 49.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [49]

    The Results section (page unavailable) reports higher CAF scores and increased FAP and MMP11 expression in fibroblasts co-cultured with UPP1-overexpressing tumor cells, not TBX3-overexpressing cells. It explicitly calls the increase in the proportion of MMP11+ CAF-like fibroblasts significant, but does not use that wording for the score and marker comparisons. (LLM, conf=0.88)

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Authors
Li, Y., Jiang, M., Aye, L., Luo, L., Zhang, Y., Xu, F., Wei, Y., Peng, D., He, X., Gu, J., Yu, X., Li, G., Ge, D., & Lu, C.
Affiliations
  • Fudan University (CN)
  • Third People's Hospital of Chengdu (CN)
  • Shanghai Medical College of Fudan University (CN)
Corresponding author
  • Li, Guoping
  • Ge, Di
  • Lu, Chunlai
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-02-08
Volume
15
Issue
1
Pages
1200-1200
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-45340-w
PMC
PMC10853547
OpenAlex
W4391644125
Cited by
71
References
11
Citations by year
2026: 22 · 2025: 39 · 2024: 10
FWCI
12.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
the Chengdu High-level Key Clinical Specialty Construction Project
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
Keywords
UPP1, lung adenocarcinoma, tumor microenvironment, immunosuppression, TGF-β1, PD-L1, PI3K/AKT/mTOR pathway, CD8+ T cell suppression, tumor-infiltrating immune cells, patient-derived organoids, tyrosine kinase inhibitors, bosutinib, dasatinib, prognostic factors, single-cell RNA sequencing
MeSH terms
Adenocarcinoma of Lung, Humans, Immunosuppressive Agents, Lung Neoplasms, Uridine Phosphorylase, Cytokines, CD8-Positive T-Lymphocytes, Phosphatidylinositol 3-Kinases, Tumor Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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