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Purpose Based on the tumor-promoting features of extracellular vesicles (EV) and PD-L1/2-bearing EV subpopulations (PD-L1/2 EV ), we evaluated their potential as surrogate markers for disease progression or eligibility criteria for PD-1 immune checkpoint inhibition (ICI) approaches in early triple-negative breast cancer (TNBC). Methods After enrichment of EV from plasma samples of 56 patients before and 50 after chemotherapy (CT), we determined levels of EV particle number and PD-L1/2 EV  by nanoparticle tracking analysis or ELISA and associated the results with clinical status/outcome and the presence of distinct circulating tumor cells (CTC) subpopulations. Results Compared to healthy controls, patients had a tenfold higher EV concentration and significantly elevated PD L2 EV  but not PD L1 EV  levels. The most important clinical implications were found for PD-L2 EV . High PD-L2 EV  levels were associated with a significantly reduced 3-year progression-free and overall survival (PFS and OS). A loss of PD-L2 EV  after CT was significantly more prominent in patients achieving pathological complete response (pCR). Increased pre-CT PD-L2 EV  levels were found in patients having NOTCH1-positive or ERBB3-positive CTC. The presence of ERBB3-positive CTC combined with high pre-CT PD-L2 EV  resulted in a shorter PFS. Conclusion This study highlights PD L2 EV  as a promising biomarker for risk assessment of TNBC patients and represents the basic for additional studies introducing PD-L2 EV  as an eligibility criterion for PD-1 ICI approaches.

journal of cancer research and clinical oncology

Programmed death receptor ligand-2 (PD-L2) bearing extracellular vesicles as a new biomarker to identify early triple-negative breast cancer patients at high risk for relapse