In:
Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 149, No. 3 ( 2023-03), p. 1159-1174
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0171-5216
,
1432-1335
DOI:
10.1007/s00432-022-03980-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
1459285-X
