Multimodal Transcriptomic Profiling of T Cell Responses to Triple-Negative Breast Cancer-Derived Exosomes

Triple-negative breast cancer (TNBC) is a highly aggressive and immunogenic subtype that lacks effective targeted therapies. Although tumor-derived exosomes are known to influence immune responses, their direct role in shaping human T cell plasticity and antigen specificity remains insufficiently characterized. In this study, we performed an integrative single-cell multiomic analysis of primary human T cells following exposure to exosomes isolated from 17 genomically distinct TNBC cell lines. By combining single-cell transcriptomics, T cell receptor (TCR) V(D)J sequencing, non-coding RNA profiling, and both bulk and single-cell cytokine analyses, we identified conserved and subtype-specific immunoregulatory programs elicited by TNBC-derived exosomes.