•High intra-epithelial TILs clonality reflect tumor-antigen specific expansion and predicts favorable immunotherapy response in TNBC.•The high CTR score reflects an immunosuppressive TME characterized by suppressed CD8+ T cell function.•High DDIT3 expression increases Tregs infiltration, promoting an immunosuppressive TME.•Follicular helper T cells are more abundant in tumor cell-enriched regions.•The function of CD8+ T cells is regulated by the OTUD4/CD73 axis, suppressing cytotoxicity and promoting tumor immune escape. Here, OTUD4 is linked to neoplasm.