Systemic chemotherapy in metastatic TNBC polarizes effector T cell differentiation.

Background: 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.

Methods: 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: 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.

Conclusion: 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.