Metabolic Reprogramming of T Cells by Dual UCP2 and IL-17 Blockade Enhances Immunity Against Pancreatic Cancer.
1/5 보강
Pancreatic ductal adenocarcinoma (PDAC) remains resistant to immunotherapy due to its immunosuppressive tumor microenvironment (TME) and impaired metabolic fitness of effector T cells.
APA
Liu CT, Yeh CC, et al. (2026). Metabolic Reprogramming of T Cells by Dual UCP2 and IL-17 Blockade Enhances Immunity Against Pancreatic Cancer.. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(16), e13020. https://doi.org/10.1002/advs.202513020
MLA
Liu CT, et al.. "Metabolic Reprogramming of T Cells by Dual UCP2 and IL-17 Blockade Enhances Immunity Against Pancreatic Cancer.." Advanced science (Weinheim, Baden-Wurttemberg, Germany), vol. 13, no. 16, 2026, pp. e13020.
PMID
41486584 ↗
Abstract 한글 요약
Pancreatic ductal adenocarcinoma (PDAC) remains resistant to immunotherapy due to its immunosuppressive tumor microenvironment (TME) and impaired metabolic fitness of effector T cells. Here, we show that targeting UCP2 reprograms T-cell metabolism, and that dual blockade with IL-17 further enhance antitumor responses in PDAC. Pharmacologic UCP2 inhibition with genipin increases IFN-γ production by CD8⁺ T cells through IL-12R/STAT4/mTOR signaling and enhanced mitochondrial oxidative phosphorylation, promoting a T-bet-driven cytotoxic program. However, UCP2 inhibition alone does not suppress tumor growth. Accordingly, combination with IL-17 depletion synergistically augments Tc1/Th1 responses, reduces myeloid-derived suppressor cells (MDSCs), and improves survival across multiple PDAC models, including genetically engineered and orthotopic systems. CD8⁺ T-cell depletion abrogates these effects. Moreover, UCP2 inhibition enhances IFN-γ production in patient-derived PBMCs and tumor-infiltrating lymphocytes. These findings identify UCP2 as a metabolic checkpoint in cytotoxic T cells and support dual UCP2/IL-17 blockade as a promising immunotherapeutic strategy for PDAC.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Uncoupling Protein 2
- Pancreatic Neoplasms
- Animals
- Interleukin-17
- Mice
- Humans
- Carcinoma
- Pancreatic Ductal
- Tumor Microenvironment
- Cell Line
- Tumor
- CD8-Positive T-Lymphocytes
- T-Lymphocytes
- Immunotherapy
- Metabolic Reprogramming
- cytotoxic T cell
- immunotherapy
- interleukin‐17
- pancreatic cancer
- uncoupling protein 2
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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