ArticleBMC biology2021
Single-cell transcriptomics reveals the effect of PD-L1/TGF-β blockade on the tumor microenvironment.
Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- TGF‑β1 in cancer: From tumour suppressor to promoter, molecular mechanisms, and precision therapeutic strategies (Review).International journal of oncology · 2026Review
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Targeting inflammatory microenvironments: overcoming therapy resistance and immunosuppression.Molecular cancer · 2026Review
- Cancer-associated fibroblast heterogeneity and its role in reshaping immunotherapy in solid cancers: potential strategies and clinical promise.Frontiers in cell and developmental biology · 2026Review
- Crosstalk between tumor-associated macrophages and the B7/CD28 family in immune checkpoint inhibitor-induced immunotherapy.Molecular and cellular biochemistry · 2026Review
- A computational analysis of programmed cell death-associated LncRNA signatures in glioma and drug prediction.BMC neurology · 2025Article
- The fibroinflammatory response in cancer.Nature reviews. Cancer · 2025Review
- Spatial genomics reveals cholesterol metabolism as a key factor in colorectal cancer immunotherapy resistance.Frontiers in oncology · 2025Article
- Targeting heterogeneous tumor microenvironments in pancreatic cancer mouse models of metastasis by TGF-β depletion.JCI insight · 2024Article
- Tumor associated macrophages as key contributors and targets in current and future therapies for melanoma.Expert review of clinical immunology · 2024Review
- M2-type tumor-associated macrophages upregulated PD-L1 expression in cervical cancer via the PI3K/AKT pathway.European journal of medical research · 2024Article
- Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors.Nature communications · 2023Article
- Artificial Intelligence-Assisted Transcriptomic Analysis to Advance Cancer Immunotherapy.Journal of clinical medicine · 2023Review
- The difficulty in translating the preclinical success of combined TGFβ and immune checkpoint inhibition to clinical trial.EBioMedicine · 2022Review
- Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Next-generation immunotherapy for solid tumors: combination immunotherapy with crosstalk blockade of TGFβ and PD-1/PD-L1.Expert opinion on investigational drugs · 2022Article
- Cancer-associated fibroblasts in the single-cell era.Nature cancer · 2022Review
- Clinical and molecular assessment of an onco-immune signature with prognostic significance in patients with colorectal cancer.Cancer medicine · 2022Article
- Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression.Frontiers in immunology · 2022Review
- Comprehensive Analysis of the Immune Cell Infiltration Landscape and Immune-Related Methylation in Retinoblastoma.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe anti-tumor activity of anti-PD-1/PD-L1 therapies correlates with T cell infiltration in tumors. Thus, a major goal in oncology is to find strategies that enhance T cell infiltration and efficacy of anti-PD-1/PD-L1 therapy. TGF-β has been shown to contribute to T cell exclusion, and anti-TGF-β improves anti-PD-L1 efficacy in vivo. However, TGF-β inhibition has frequently been shown to induce toxicity in the clinic, and the clinical efficacy of combination PD-L1 and TGF-β blockade has not yet been proven. To identify strategies to overcome resistance to PD-L1 blockade, the transcriptional programs associated with PD-L1 and/or TGF-β blockade in the tumor microenvironment should be further elucidated.
resultsWe used single-cell RNA sequencing in a mouse model to characterize the transcriptomic effects of PD-L1 and/or TGF-β blockade on nearly 30,000 single cells in the tumor and surrounding microenvironment. Combination treatment led to upregulation of immune response genes, including multiple chemokine genes such as CCL5, in macrophages, and downregulation of extracellular matrix genes in fibroblasts. Analysis of publicly available tumor transcriptome profiles showed that the chemokine CCL5 was strongly associated with immune cell infiltration in various human cancers. Further investigation with in vivo models showed that intratumorally administered CCL5 enhanced cytotoxic lymphocytes and the anti-tumor activity of anti-PD-L1.
conclusionsTaken together, our data could be leveraged translationally to complement or find alternatives to anti-PD-L1 plus anti-TGF-β combination therapy, for example through companion biomarkers, and/or to identify novel targets that could be modulated to overcome resistance.
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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.