Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer

Diego de Miguel-Perez, Alessandro Russo, Oscar Arrieta, Murat Ak, Feliciano Barron, Muthukumar Gunasekaran, Priyadarshini Mamindla, Luis Lara-Mejia, Christine B. Peterson, Mehmet E. Er, Vishal Peddagangireddy, Francesco Buemi, Brandon Cooper, Paolo Manca, Rena G. Lapidus, Ru Ching Hsia, Andres F. Cardona, Aung Naing, Sunjay Kaushal, Fred R. HirschPhilip C. Mack, Maria Jose Serrano, Vincenzo Adamo, Rivka R. Colen, Christian Rolfo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods: Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results: As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion: These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.

Original languageEnglish (US)
Article number186
JournalJournal of Experimental and Clinical Cancer Research
Volume41
Issue number1
DOIs
StatePublished - Dec 2022
Externally publishedYes

Keywords

  • Biomarkers
  • Extracellular vesicles
  • Immunotherapy
  • NSCLC
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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