Year: 2025
Type: article
Abstract: Description While cancer cells adapt to the tumor environment by maintaining a low level of differentiation despite high proliferation, T lymphocytes undergo terminal differentiation. One of the unique adaptive mechanisms in tumors is the epithelial-to-mesenchymal transition (EMT). We identified that the EMT gene Snail1 may also be expressed by effector CD8+ T cells, and IL-2 maintains its expression via STAT5 and GSK-3. Snail1 enhances T cell persistence and stabilizes their effector phase by enhancing the β-catenin pathway. Snail1 expression in CD8+ T cells is associated with increased anti-tumor immunity in animal models and correlates with the efficacy of immune checkpoint blockade in cancer patients. Treatment with H9T, an engineered IL-2 partial agonist, enhances Snail1-dependent T cell immunity in vivo. Snail1-expressing CAR-T cells show superior persistence and anti-tumor activity in preclinical models. Thus, Snail1 is a potential target for cancer immunotherapy. Funding Sources CA248430 Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)
Source: The Journal of Immunology
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416447340
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