ArticleJournal for immunotherapy of cancer2021
Phosphorylation of SMAD3 in immune cells predicts survival of patients with early stage non-small cell lung cancer.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- The Treg-cell death axis in lung cancer: implications for immune evasion and novel therapeutic strategies.Molecular cancer · 2026Review
- GARP-expressing Tregs as a source of immunosuppressive TGF-β1 in human tumors.Cancer immunology, immunotherapy : CII · 2025Article
- SMAD2 linker phosphorylation impacts overall survival, proliferation, TGFβ1-dependent gene expression and pluripotency-related proteins in NSCLC.British journal of cancer · 2025Article
- Article
- Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer.Journal of translational medicine · 2024Article
- Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-β.International journal of chronic obstructive pulmonary disease · 2024Article
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma.Nature communications · 2023Article
- MK2 drives progression of pancreas and colon cancers by suppressing CD8Frontiers in immunology · 2023Article
- Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis.Frontiers in oncology · 2023Article
- Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy.SAGE open medicine · 2022Review
- Identification of CDK2-Related Immune Forecast Model and ceRNA in Lung Adenocarcinoma, a Pan-Cancer Analysis.Frontiers in cell and developmental biology · 2021Article
- Relation of Osteopontin Expression to Tumor-Associated Macrophages-Derived Transforming Growth Factor Beta 1 Expression in Non-small Cell Lung Carcinoma.Journal of microscopy and ultrastructureArticle
- Prognostic Significance of TLR2, SMAD3 and Localization-dependent SATB1 in Stage I and II Non-Small-Cell Lung Cancer Patients.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe interplay of immune and cancer cells takes place in the tumor microenvironment where multiple signals are exchanged. The transforming growth factor beta (TGFB) pathway is known to be dysregulated in lung cancer and can impede an effective immune response. However, the exact mechanisms are yet to be determined. Especially which cells respond and where does this signaling take place with respect to the local microenvironment.
methodsHuman non-small cell lung cancer samples were retrospectively analyzed by multiplexed immunohistochemistry for SMAD3 phosphorylation and programmed death ligand 1 expression in different immune cells with respect to their localization within the tumor tissue. Spatial relationships were studied to examine possible cell-cell interactions and analyzed in conjunction with clinical data.
resultsTGFB pathway activation in CD3, CD8, Foxp3 and CD68 cells, as indicated by SMAD3 phosphorylation, negatively impacts overall and partially disease-free survival of patients with lung cancerindependent of histological subtype. A high frequency of Foxp3 regulatory T cells positive for SMAD3 phosphorylation in close vicinity of CD8 T cells within the tumor discriminate a rapidly progressing group of patients with lung cancer.
conclusionsTGFB pathway activation of local immune cells within the tumor microenvironment impacts survival of early stage lung cancer. This might benefit patients not eligible for targeted therapies or immune checkpoint therapy as a therapeutic option to re-activate the local immune response.
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