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Expression of Immunomodulatory Checkpoint Molecules in Drug-Resistant Neuroblastoma: An Exploratory Study

Nicholas J Skertich1, Fei Chu1, Imad A M Tarhoni2,3

  • 1Department of Surgery, Division of Pediatric Surgery, Rush University Medical Center, Chicago, IL 60612, USA.

Cancers
|February 15, 2022
PubMed

Insights

Neuroblastoma, a childhood cancer, shows PD-L1 expression in resistant cells. This suggests PD-L1 as a potential therapeutic target, though its role in drug resistance requires further investigation.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Neuroblastoma is a prevalent childhood cancer with a poor prognosis in advanced stages.
  • Checkpoint molecule inhibition has shown success in treating advanced adult cancers.

Purpose of the Study:

  • To investigate the expression of PD-L1 and other checkpoint molecules in neuroblastoma.
  • To determine their roles in drug resistance and potential as therapeutic targets.

Main Methods:

  • Developed doxorubicin-resistant (DoxR) neuroblastoma cell lines.
  • Utilized in vitro invasion assays, Western blot, and immuno-oncology checkpoint protein panels.
  • Quantified 17 checkpoint molecules in cellular and soluble fractions.

Main Results:

  • PD-L1 and 12 other checkpoint molecules were present in all cell lysates without significant level differences.
  • Three checkpoint molecules were found to be soluble in the cell media.
  • PD-L1 was expressed in both DoxR and parental neuroblastoma cells.

Conclusions:

  • PD-L1 is expressed in neuroblastoma cells and represents a potential therapeutic target.
  • The specific role of PD-L1 in neuroblastoma drug resistance remains unclear.
  • Benchmarking checkpoint molecules aids in identifying future therapeutic targets and biomarkers.
Keywords:
checkpoint molecule inhibitioncheckpoint protein moleculesdoxorubicindrug resistanceneuroblastomaprogrammed death ligand 1

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