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IL-15 Superagonists for Reprogramming the Immunosuppressive Microenvironment in Gastrointestinal Adenocarcinomas
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DOI：10.1016/j.canlet.2026.218780.png)
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Abstract
En 中文
• IL-15 superagonists enhance NK and CD8+ T-cell antitumor activity. • Stromal and cytokine barriers drive immune exclusion in GI adenocarcinomas. • TGF-β and IL-10 blockade improves IL-15 therapeutic efficacy. • Local cytokine delivery improves tumor targeting and reduces toxicity. • IL-15 strategies may convert immune-cold tumors into responsive tumors.
Keywords:
IL-15 Superagonist
Gastrointestinal Adenocarcinoma
Tumor Microenvironment
Immune Modulation
Cytokine Therapy
Natural Killer and CD8+ T-cells
CAF
Cancer-Associated Fibroblast
CRS
Cytokine Release Syndrome
DC
Dendritic Cells
ECM
Extracellular Matrix
EUS
Endoscopic Ultrasound
GC
Gastric Cancer
GI
Gastrointestinal
HCC
Hepatocellular Carcinoma
IFN-γ
Interferon-Gamma
IL-2
Interleukin-2
IL-6
Interleukin-6
IL-10
Interleukin-10
IL-15
Interleukin-15
JAK
Janus Kinase
LNP
Lipid Nanoparticle
MDSC
Myeloid-Derived Suppressor Cell
mTOR
Mechanistic Target of Rapamycin
MSI-H/dMMR
Microsatellite Instability-High/DNA Mismatch Repair-Deficient
NK
Natural Killer Cells
NIZ985
Heterodimeric IL-15/IL-15Rα Complex
NKTR-255
PEGylated IL-15 Superagonist
PD-1
Programmed Cell Death Protein-1
PD-L1
Programmed Death-Ligand-1
PEG-PCL
Poly(ethylene glycol)–Poly(ε-caprolactone)
PK
Pharmacokinetics
RLI (SO-C101)
IL-15/IL-15Rα Sushi Domain Fusion
STAT3/STAT5
Signal Transducer and Activator of Transcription-3/5
TGF-β
Transforming Growth Factor-β
TIL
Tumor-Infiltrating Lymphocyte
TME
Tumor Microenvironment
TNBC
Triple-Negative Breast Cancer
VEGF
Vascular Endothelial Growth Factor
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