STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities
- 1Tianjin University of Traditional Chinese Medicine, College of Traditional Chinese Medicine
- 2Department of Colorectal Surgery, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University
- 3Tianjin Institute of Coloproctology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Nankai University
Abstract
Immune escape remains a major barrier to durable cancer immunotherapy. Although checkpoint blockade has transformed cancer treatment, resistance commonly reflects broader tumor-intrinsic and microenvironmental programs that sustain immune dysfunction. At this interface, STAT3 emerges as a central organizing node. Beyond its canonical role in inflammatory and oncogenic signaling, STAT3 links tumor cell plasticity, immune suppression, and metabolic adaptation across the tumor ecosystem. In tumor cells, STAT3 promotes stemness, survival, checkpoint ligand expression, impaired antigen presentation, and immunosuppressive secretomes. In immune compartments, it drives regulatory T cell expansion, myeloid-derived suppressor cell accumulation, tumor-associated macrophage polarization, and dendritic cell dysfunction, thereby stabilizing an immune-resistant niche. STAT3 also reinforces immune escape through metabolic rewiring and multicellular feed-forward circuits. These features make STAT3 an attractive but challenging therapeutic target. Here, we discuss how STAT3 functions at the tumor-immune interface to coordinate immune escape and highlight therapeutic opportunities for targeting this axis in cancer.
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BibTeX
@article{cheng2026stat3,
title = {{STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities}},
author = {Xuanya Cheng and Haoren Jing and Mingqing Zhang},
journal = {Frontiers in Immunology},
year = {2026},
month = may,
doi = {10.3389/fimmu.2026.1850359},
url = {https://doi.org/10.3389/fimmu.2026.1850359},
note = {CC BY},
}
RIS
TY - JOUR
TI - STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities
AU - Xuanya Cheng
AU - Haoren Jing
AU - Mingqing Zhang
PY - 2026
DA - 2026/05/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1850359
UR - https://doi.org/10.3389/fimmu.2026.1850359
AB - Immune escape remains a major barrier to durable cancer immunotherapy. Although checkpoint blockade has transformed cancer treatment, resistance commonly reflects broader tumor-intrinsic and microenvironmental programs that sustain immune dysfunction. At this interface, STAT3 emerges as a central organizing node. Beyond its canonical role in inflammatory and oncogenic signaling, STAT3 links tumor cell plasticity, immune suppression, and metabolic adaptation across the tumor ecosystem. In tumor cells, STAT3 promotes stemness, survival, checkpoint ligand expression, impaired antigen presentation, and immunosuppressive secretomes. In immune compartments, it drives regulatory T cell expansion, myeloid-derived suppressor cell accumulation, tumor-associated macrophage polarization, and dendritic cell dysfunction, thereby stabilizing an immune-resistant niche. STAT3 also reinforces immune escape through metabolic rewiring and multicellular feed-forward circuits. These features make STAT3 an attractive but challenging therapeutic target. Here, we discuss how STAT3 functions at the tumor-immune interface to coordinate immune escape and highlight therapeutic opportunities for targeting this axis in cancer.
SN - 1664-3224
ER -