Immunotherapy in gastrointestinal stromal tumors: Current landscape and future horizons

Gastrointestinal stromal tumors (GISTs) feature a unique tumor microenvironment (TME) with abundant immune infiltrates, including CD8+ T cells and tertiary lymphoid structures, alongside significant immune escape mechanisms such as indoleamine 2,3-dioxygenase (IDO) overexpression, MHC I loss, and regulatory T-cell activity. These factors contribute to an immunosuppressive TME, limiting the effectiveness of immune responses. Recent proteomic and immune profiling has identified distinct immune clusters, ranging from highly infiltrated "hot" tumors to immune-desert "cold" tumors, offering new insights into immune heterogeneity and prognostic stratification. While tyrosine kinase inhibitors (TKIs) like imatinib have shown immunomodulatory effects, clinical trials with immune checkpoint inhibitors (ICIs) alone or in combination have yielded modest outcomes. This editorial examines the immunologic landscape of GIST, explores the interplay between ICIs and TKIs, and highlights emerging therapeutic strategies such as IDO inhibition, bispecific antibodies, and patient selection based on TME characteristics. These insights pave the way for more effective immunotherapy approaches in GIST.