ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting IGF1R Overcomes Armored and Cold Tumor Microenvironment and Boosts Immune Checkpoint Blockade in Triple-Negative Breast Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Review
- Igniting cold tumors: reprogramming the tumor immune microenvironment with dual-payload ADCs in combination with PD-L1&4-1BB bispecific antibodies.Journal for immunotherapy of cancer · 2026Article
- Micropeptide colorectal neoplasia differentially expressed (CRNDE) 84aa encoded by CRNDE elicits a T-cell immune response to breast cancer.Translational cancer research · 2026Article
- Bidirectional Interactions Between Immune Regulation and the Insulin-like Growth Factor Axis in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Beyond the membrane: Internalization and compartmentalization of insulin‑like growth factor 1 receptor signaling in cancer pathogenesis and treatment (Review).International journal of oncology · 2026Review
- Integrated multi-regional multiomic profiling of breast phyllodes tumours reveals peritumoural immune activation and stromal remodelling.Clinical and translational medicine · 2026Article
- The role of programmed cell death 1 in autoimmune diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Emerging Nanozyme Strategies for Precision Breast Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Targeting IGF1R Overcomes Armored and Cold Tumor Microenvironment and Boosts Immune Checkpoint Blockade in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dual roles of innate immune cells and cytokines in shaping the breast cancer microenvironment.Frontiers in immunology · 2025Review
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Authors and funding
9 authors.
Funding
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Abstract
In the previous study, patients with tumors based on collagen deposition and immunoreactivity are classified and identified the armored & cold subtype as the most treatment-refractory tumor type. Triple-negative breast cancer (TNBC) is the most lethal tumor type globally, making it critical to overcome the armored and cold tumor microenvironment (TME) for effective treatment of these patients. In this study, the transcriptomic collagen activity and immune profiles of cancer patients treated with immune checkpoint blockade (ICB) are analyzed, and found that intratumoral collagen is associated with an unfavorable immunotherapeutic response and T cell exhaustion. Additionally, collagen is shown to regulate IGF1R expression at both transcriptional and post-translational levels via SOX4 and DDR1, respectively. It is also found that IGF1R promotes tumor cell migration and invasion, as well as T cell exhaustion, with these effects mediated through collagen. Moreover, in vivo inhibition of IGF1R reversed the armored & cold TME, thereby enhancing anti-PD-1 therapy. In conclusion, this study identified IGF1R as a novel therapeutic target for the immuno-collagenic subtype, and combining IGF1R inhibition with anti-PD-1 therapy provides a promising foundation for a novel combination immunotherapy regimen for TNBC.
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