Liquid Biopsy for GBM Immune Evasion By Plasmonic Biosensing of Exosomal PD-L1 and PD1 from Glioblastoma Cells and Their Associated Microglia

Glioblastoma (GBM) is known as the most fatal brain tumor with lack of an early diagnosis method,  thus urgently demanding the establishment of a reliable and precise liquid biopsy method for GBM pre-screening and prognosis using a sensitive biosensor and a faithful GBM biomarker.GBM  formation and progression  is promoted by multiple mechanisms.  GBM  cells  (GMs)’glycolytic reprogramming is essential for tumor survival and growth, consequently leading to the high production of lactate and the upregulation of lactate transporters,  MCT1/4.Furthermore, it promotes exosome secretion and exosome-mediated interactions with GBM-associated  microglia/macrophages  (GAMs),  comprising  30-50%  populations  of  cells  in  the GBM,  for  tumor  progression.  Particularly,  immune evasion by  PD-L1  upregulation in  GMs and their daughter exosomes,  and its interaction with  PD1  in invaded  T  cells in the lactate-enriched tumor microenvironment is essential for tumor progression. Therefore, this study aims to determine whether GMs- and GAMs-derived exosomes contain PD-L1 or PD1 which can be sensitively detected by a label-free plasmonic biosensor. With use of an Au-Pt plasmonic biosensor and two orthotopic mouse models of GBM, this study demonstrates the feasibility and reliability of a plasmonic biosensor-based detection of GMs- and GAMs-derived exosomal PD-L1/PD1 as liquid biopsy for GBM immune evasion in vivo.