TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1 macrophages.
1/5 보강
Transforming growth factor β (TGF-β) signaling in the tumor microenvironment predicts resistance to immune checkpoint blockade (ICB).
APA
Henriques A, Salvany-Celades M, et al. (2025). TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1 macrophages.. Nature genetics, 57(12), 3050-3065. https://doi.org/10.1038/s41588-025-02380-2
MLA
Henriques A, et al.. "TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1 macrophages.." Nature genetics, vol. 57, no. 12, 2025, pp. 3050-3065.
PMID
41203813 ↗
Abstract 한글 요약
Transforming growth factor β (TGF-β) signaling in the tumor microenvironment predicts resistance to immune checkpoint blockade (ICB). While TGF-β inhibition enhances ICB efficacy in murine cancer models, clinical trials have yet to demonstrate benefit, underscoring the need to better understand its immunoregulatory roles across disease contexts. Using mouse models of advanced colorectal cancer and patient-derived data, we demonstrate that TGF-β impairs antitumor immunity at multiple levels in liver metastases. It acts directly on T cells to block recruitment of peripheral memory CD8 T cells, thereby limiting the effectiveness of ICB. Concurrently, TGF-β instructs tumor-associated macrophages to suppress clonal expansion of newly arrived T cells by inducing SPP1 expression. This extracellular matrix protein promotes collagen deposition and accumulation of tumor-associated macrophages and fibroblasts, ultimately driving ICB resistance. Our findings reveal how TGF-β coordinates immunosuppressive mechanisms across innate and adaptive immune compartments to promote metastasis, offering new avenues to improve immunotherapy in colorectal cancer.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
- SpNeigh: spatial neighborhood and differential expression analysis for high-resolution spatial transcriptomics.
- Key Considerations for Targeting in Pancreatic Cancer: Potential Impact on the Treatment Paradigm.
- EXPLORING THE IMPACT OF GUT MICROBIOTA MODULATION ON COLORECTAL CANCER THERAPY: A BIBLIOMETRIC ANALYSIS OF PROBIOTIC AND PREBIOTIC INTERVENTIONS.
- The tumor microenvironment as a key regulator of radiotherapy response.
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.
- Advances in green-synthesized magnetic nanoparticles for targeted cancer therapy: mechanisms, applications, and future perspectives.