PD‐L1 on large extracellular vesicles is a predictive biomarker for therapy response in tissue PD‐L1‐low and ‐negative patients with non‐small cell lung cancer

2024 | journal article. A publication with affiliation to the University of Göttingen.

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​PD‐L1 on large extracellular vesicles is a predictive biomarker for therapy response in tissue PD‐L1‐low and ‐negative patients with non‐small cell lung cancer​
Schöne, N.; Kemper, M.; Menck, K.; Evers, G.; Krekeler, C.; Schulze, A. B. & Lenz, G. et al.​ (2024) 
Journal of Extracellular Vesicles13(3) art. e12418​.​ DOI: https://doi.org/10.1002/jev2.12418 

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Authors
Schöne, Nadja; Kemper, Marcel; Menck, Kerstin; Evers, Georg; Krekeler, Carolin; Schulze, Arik Bernard; Lenz, Georg; Wardelmann, Eva; Binder, Claudia; Bleckmann, Annalen
Abstract
Abstract Immunotherapy has revolutionized the treatment of patients with non‐small cell lung cancer (NSCLC). High expression of tissue PD‐L1 (tPD‐L1) is currently the only approved biomarker for predicting treatment response. However, even tPD‐L1 low (1‐49%) and absent (<1%) patients might benefit from immunotherapy but, to date, there is no reliable biomarker, that can predict response in this particular patient subgroup. This study aimed to test whether tumour‐associated extracellular vesicles (EVs) could fill this gap. Using NSCLC cell lines, we identified a panel of tumour‐related antigens that were enriched on large EVs (lEVs) compared to smaller EVs. The levels of lEVs carrying these antigens were significantly elevated in plasma of NSCLC patients ( n  = 108) and discriminated them from controls ( n  = 77). Among the tested antigens, we focused on programmed cell death ligand 1 (PD‐L1), which is a well‐known direct target for immunotherapy. In plasma lEVs, PD‐L1 was mainly found on a population of CD45 − /CD62P + lEVs and thus seemed to be associated with platelet‐derived vesicles. Patients with high baseline levels of PD‐L1 + lEVs in blood showed a significantly better response to immunotherapy and prolonged survival. This was particularly true in the subgroup of NSCLC patients with low or absent tPD‐L1 expression, thus identifying PD‐L1‐positive lEVs in plasma as a novel predictive and prognostic marker for immunotherapy.
Issue Date
2024
Journal
Journal of Extracellular Vesicles 
ISSN
2001-3078
eISSN
2001-3078
Language
English

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