biostudies-literatureWang YJoint Funds for the Innovation of Science and Technology, Fujian ProvinceGuangdong Basic and Applied Basic Research Foundation Key ProjectScience and Technology Special Fund of Guangdong Province of Chinathe National Natural Science Foundation of China youth science fund projects51https://www.ebi.ac.uk/biostudies/studies/S-EPMC11969778biostudies-literatureUnknown27(1)Neoadjuvant checkpoint blockade immunotherapy (NATI) significantly prolonged outcomes for triple-negative breast cancer (TNBC). Residual tumor cells that survive NATI represent high-risk cell populations with metastatic potential and usually evade immunosurveillance by NK cells. Using an 82-protein panel, we here profiled single-cell membrane proteomics of CD56+ (NCAM1+) NK cells from tumor, peri-cancerous tissue, as well as peripheral blood from 28 TNBC patients post-NATI of residual cancer burden II/III. Unsupervised clustering resulted in several distinct clusters: 2 tumor-infiltrating NK (TINK) clusters with divergent functions of immune activation (TNFRSF7+) and suppression (SELL+); 2 immuno-suppressive peri-cancerous clusters; and 1 periphery-specific cluster. Considering the contradBreast cancer research : BCRPhenotypes and cytokines of NK cells in triple-negative breast cancer resistant to checkpoint blockade immunotherapy.PMC119697782023Y90542023B1515230004STKJ202300282102687Ding FLi JLyu XMa YChen BJiang YZhu PHuang TZheng HHe TQi XLu JNiu YSZeng JZhong GWang WWang XLin JWang YXu YfalsePhenotypes and cytokines of NK cells in triple-negative breast cancer resistant to checkpoint blockade immunotherapy.Neoadjuvant checkpoint blockade immunotherapy (NATI) significantly prolonged outcomes for triple-negative breast cancer (TNBC). Residual tumor cells that survive NATI represent high-risk cell populations with metastatic potential and usually evade immunosurveillance by NK cells. Using an 82-protein panel, we here profiled single-cell membrane proteomics of CD56+ (NCAM1+) NK cells from tumor, peri-cancerous tissue, as well as peripheral blood from 28 TNBC patients post-NATI of residual cancer burden II/III. Unsupervised clustering resulted in several distinct clusters: 2 tumor-infiltrating NK (TINK) clusters with divergent functions of immune activation (TNFRSF7+) and suppression (SELL+); 2 immuno-suppressive peri-cancerous clusters; and 1 periphery-specific cluster. Considering the contrad2025-01-01T00:00:00Z2025 Apr2025-07-01T03:05:23.164Z2025-07-01T03:05:23.164ZS-EPMC119697784018142610.1186/s13058-025-02003-y