ArticleJCI insight2021
Hedgehog-induced PD-L1 on tumor-associated macrophages is critical for suppression of tumor-infiltrating CD8+ T cell function.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 96 citations in OpenAlex.
- Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Biomimetic co-delivery nanoplatform overcomes CAF- and TAM-induced immunosuppression to augment therapeutic efficacy against triple-negative breast cancer.International journal of pharmaceutics: X · 2026Article
- Dedifferentiation in endometrial cancer is associated with HLA-I silencing that may be restored by IFN-γ.The Journal of pathology · 2026Article
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- Dual Role of Tamoxifen in Enhancing STING and CEACAM1 Expression to Prime a Favorable Tumor Microenvironment for Anti-TIM3 Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Bioinformatics mining and clinical validation of CD274 as a prognostic indicator in hepatocellular carcinoma.BMC cancer · 2026Article
- Article
- MTFR2 promotes VDAC1 oligomerization to reprogram BCAA metabolism in tumor cells to polarize TAMs in LUAD.Cell death & disease · 2026Article
- Single-cell transcriptomics reveals FXR1 as an actionable target for siRNA therapy in ovarian cancer.Nature communications · 2026Article
- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- Clinical applications of immunogenomics in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Targeting Tumor-Associated Macrophages and Cancer-Associated Fibroblasts to Overcome Therapeutic Resistance in Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Graph neural network modeling of spatial tumor-immune interactions identifies prognostic cellular niches in non‑small cell lung cancer.NPJ precision oncology · 2026Article
- Cathepsins in prostate cancer: multifunctional regulators in tumor progression and therapeutic prospects-a narrative review.Translational andrology and urology · 2026Review
- Review
- T-cell-targeted immunotherapy in neurofibromatosis type 2-related vestibular schwannoma: current evidence and future direction.Brain communications · 2026Review
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Myeloid-derived PD-L1 characterizes spatially organized immune architecture in colorectal cancer.Frontiers in immunology · 2026Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The programmed death-1 (PD-1) and the PD ligand 1 (PD-L1) interaction represents a key immune checkpoint within the tumor microenvironment (TME), and PD-1 blockade has led to exciting therapeutic advances in clinical oncology. Although IFN-γ-dependent PD-L1 induction on tumor cells was initially thought to mediate the suppression on effector cells, recent studies have shown that PD-L1 is also expressed at high level on tumor-associated macrophages (TAMs) in certain types of tumors. However, the precise role of PD-L1 expression on TAMs in suppressing antitumor immunity within the TME remains to be defined. Using a myeloid-specific Pdl1-knockout mouse model, here we showed definitive evidence that PD-L1 expression on TAMs is critical for suppression of intratumor CD8+ T cell function. We further demonstrated that tumor-derived Sonic hedgehog (Shh) drives PD-L1 expression in TAMs to suppress tumor-infiltrating CD8+ T cell function, leading to tumor progression. Mechanistically, Shh-dependent upregulation of PD-L1 in TAMs is mediated by signal transducer and activator of transcription 3, a cascade that has not been previously reported to our knowledge. Last, single-cell RNA sequencing analysis of human hepatocellular carcinoma revealed that PD-L1 is mainly expressed on M2 TAMs, supporting the clinical relevance of our findings. Collectively, our data revealed an essential role for Shh-dependent PD-L1 upregulation in TAMs in suppressing antitumor immunity within the TME, which could lead to the development of new immunotherapeutic strategies for treating cancer.
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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.