Regulatory T cells in gastrointestinal stromal tumor exhibit distinct features and promote tumor growth

ABSTRACT: Regulatory T cells (Tregs) are a critical component of the tumor microenvironment as they can either promote or suppress anti-tumoral immune responses. The phenotypic and transcriptional features of Tregs in gastrointestinal stromal tumor (GIST), the most common human sarcoma, have not been defined. In a genetically engineered mouse model of GIST driven by a mutation in the KIT gene, we found that intratumoral Tregs have a highly activated phenotype compared to Tregs from the tumor-draining lymph node (TDLN) or spleen. Furthermore, transcriptome profiling revealed that tumor Tregs were distinct from TDLN Tregs, particularly in genes responsible for cell migration and the immune response. Tumor cell inhibition of oncogenic KIT by imatinib altered several cytokines, chemokines, and transcription factors of tumor Tregs, but not TDLN Tregs. Systemic depletion of Tregs reduced tumor growth and increased CD8+ and conventional CD4+ T cell proliferation and effector function. However, Treg depletion did not augment the anti-tumor efficacy of imatinib, suggesting overlapping mechanisms. Our findings demonstrate that intratumoral Tregs depend on tumor cell oncogenic activity and promote tumor growth in GIST.

ORGANISM(S): Mus musculus

PROVIDER: GSE278632 | GEO | 2026/10/01

REPOSITORIES: GEO