ArticleMolecular oncology2020
Epidermal activation of Hedgehog signaling establishes an immunosuppressive microenvironment in basal cell carcinoma by modulating skin immunity.
Article in Molecular oncology, 2020. 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, 30 citations in OpenAlex.
- Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma.Nature communications · 2022Trial
- The Role of Hedgehog Signaling in Non-small Cell Lung Cancer: Targeting Tumor Invasion, Therapy Resistance and Novel Therapeutic Strategies.International journal of biological sciences · 2026Review
- Cooperative Hedgehog/GLI and JAK/STAT signaling drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer.Cell communication and signaling : CCS · 2025Article
- Exploring the relation between TGF-β pathway activity and response to checkpoint inhibition in patients with metastatic melanoma.Clinical and experimental immunology · 2025Article
- Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells.Science advances · 2025Article
- Review
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Tumor-derived GLI1 promotes remodeling of the immune tumor microenvironment in melanoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Cargo-Dependent Targeted Cellular Uptake Using Quaternized Starch as a Carrier.Nanomaterials (Basel, Switzerland) · 2023Article
- Review
- Current Landscape of Immunotherapy for Advanced Sarcoma.Cancers · 2023Review
- A drug screening to identify novel combinatorial strategies for boosting cancer immunotherapy efficacy.Journal of translational medicine · 2023Article
- Emerging Roles of Hedgehog Signaling in Cancer Immunity.International journal of molecular sciences · 2023Review
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- Topical Delivery of Hedgehog Inhibitors: Current Status and Perspectives.International journal of molecular sciences · 2022Review
- Novel Approaches in Non-Melanoma Skin Cancers-A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC).Cells · 2022Review
- Basal Cell Carcinoma and Hedgehog Pathway Inhibitors: Focus on Immune Response.Frontiers in medicine · 2022Review
- Review
- Article
- Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Genetic activation of hedgehog/glioma-associated oncogene homolog (HH/GLI) signaling causes basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer. Small molecule targeting of the essential HH effector Smoothened (SMO) has proven an effective therapy of BCC, though the frequent development of drug resistance poses major challenges to anti-HH treatments. In light of recent breakthroughs in cancer immunotherapy, we analyzed the possible immunosuppressive mechanisms in HH/GLI-induced BCC in detail. Using a genetic mouse model of BCC, we identified profound differences in the infiltration of BCC lesions with cells of the adaptive and innate immune system. Epidermal activation of Hh/Gli signaling led to an accumulation of immunosuppressive regulatory T cells, and to an increased expression of immune checkpoint molecules including programmed death (PD)-1/PD-ligand 1. Anti-PD-1 monotherapy, however, did not reduce tumor growth, presumably due to the lack of immunogenic mutations in common BCC mouse models, as shown by whole-exome sequencing. BCC lesions also displayed a marked infiltration with neutrophils, the depletion of which unexpectedly promoted BCC growth. The study provides a comprehensive survey of and novel insights into the immune status of murine BCC and serves as a basis for the design of efficacious rational combination treatments. This study also underlines the need for predictive immunogenic mouse models of BCC to evaluate the efficacy of immunotherapeutic strategies in vivo.
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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.