Systemic chemotherapy in metastatic TNBC polarizes effector T cell differentiation

Triple-negative breast cancer (TNBC) has the poorest prognosis among the three major subtypes of breast cancer, and more than one-third of patients with TNBC experience recurrence or distant metastasis. Despite advances in diverse immunotherapy strategies for metastatic TNBC (mTNBC), multiple mechanisms underlying resistance to treatment remain unknown.

In this study, the dynamic changes in the immune landscape in mTNBC were assessed and compared with healthy donors using single-cell RNA sequencing (scRNA-seq) analysis. By integrating internal and public scRNA-seq data, 61,149 cells extracted from East Asian patients with mTNBC and 51,448 cells extracted from East Asian healthy donors were used to landscape a comprehensive cellular profile of mTNBC.

Results showed that nine overexpressed genes from patients with mTNBC in effector T cells such as CTSW, PRF1, GNLY, GZMA, CCL5, KLRD1, KLRB1, B2M, and GZMB exhibited favorable survival prognoses. In addition, effector T cells enriched in patients with mTNBC were more differentiated compared with those enriched in healthy donors.

Collectively, this study is the first to provide potential diagnostic and therapeutic targets of East Asian chemotherapy-treated mTNBC with regard to effector T cells.