ArticleThe Journal of clinical investigation2019
Hedgehog signaling promotes tumor-associated macrophage polarization to suppress intratumoral CD8+ T cell recruitment.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
188 citing papers in PubMed, 2 syntheses or guidelines pooled it, 278 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- Hedgehog blockade in steroid-refractory sclerotic chronic graft-versus-host disease.British journal of haematology · 2021Trial
- 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
- Aged ZnO Nanoparticles Promote Breast Cancer Lung Metastasis by Remodeling the Pulmonary Microenvironment Through the CXCL10/Wnt/β-Catenin Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.American journal of hematology · 2026Article
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Article
- Advances in miRNA-Mediated Bidirectional Crosstalk and Immune Evasion Mechanisms Between Lung Cancer Cells and CD8International journal of molecular sciences · 2026Review
- Immunological and prognostic impact of NRF2 in high grade serous ovarian cancer.Genes and immunity · 2026Article
- Nanovesicles With Mechanically Induced Adjuvanticity for Robust Melanoma Vaccination Toward Tumor-Associated Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Spatial anchoring of lipid metabolism shapes immune fate in the tumor microenvironment.Lipids in health and disease · 2026Review
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Combined radiation andMolecular therapy. Oncology · 2026Article
- Ferroptosis as a therapeutic target in cancer: mechanisms, immune interactions, and emerging strategies.Molecular cancer · 2026Review
- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- A novel humanized immune stroma PDX cancer model for therapeutic studies.Cancer immunology, immunotherapy : CII · 2026Article
- FCRLB-mediated dual control of tumor metabolism and macrophage polarization promotes lung cancer malignancy.Journal of translational medicine · 2026Article
- LAMA1 Promotes Tumor-Associated Macrophages Polarization Towards the M2 Phenotype and Induces Colorectal Cancer.Applied biochemistry and biotechnology · 2026Article
128 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumor-associated macrophages (TAMs) usually display an antiinflammatory M2-like phenotype to facilitate tumor growth. However, what drives M2 polarization of TAMs and how TAMs suppress antitumor immunity within the tumor microenvironment (TME) remain largely undefined. Using several murine tumor models, we showed that hedgehog (Hh) signaling in myeloid cells is critical for TAM M2 polarization and tumor growth. We also found that tumor cells secrete sonic hedgehog (SHH), an Hh ligand, and that tumor-derived SHH drives TAM M2 polarization. Furthermore, Hh-induced functional polarization in TAMs suppresses CD8+ T cell recruitment to the TME through the inhibition of CXCL9 and CXCL10 production by TAMs. Last, we demonstrated that Krüppel-like factor 4 (Klf4) mediates Hh-dependent TAM M2 polarization and the immunosuppressive function. Collectively, these findings highlight a critical role for tumor-derived SHH in promoting TAM M2 polarization, a mechanism for TAM-mediated immunosuppression, and may provide insights into the design of new cancer immunotherapeutic strategies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.