Work

STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities

Year: 2026

Type: review

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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1850359

Authors: Xuanya Cheng, Haoren Jing, Mingqing Zhang

Institutions: Tianjin University of Traditional Chinese Medicine, Nankai University

Language: English

Topic: Cytokine Signaling Pathways and Interactions

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801