The single-cell transcriptome defines an effector Vd1 gd T cell-dependent anti-tumor immunity in human gastrointestinal stromal tumor (GIST)

However, the function of gd T cells in human gastrointestinal stromal tumor (GIST), the most common type of human sarcoma, is unknown. Here, we combined single-cell RNA-seq (scRNA-seq), immunophenotyping, and next-generation T-cell receptor (TCR) sequencing of sorted human circulating and intratumoral gd T cells to query their impact on tumor immunity in GIST.

We identified major subtypes of Vd1 and Vd2 cells, which were more differentiated in tumors. The effector Vd1 subset exhibited higher expression of cytotoxicity-related transcription and exhaustion molecules, and highly expressed the key transcription factors TBX21 and EOMES. Tyrosine kinase inhibitor (TKI) treatment induced the tumor-enriched Vd1 cells to undergo profound phenotype differentiation, alternative clonal expansion, and TCR diversity.