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

Cancers

Jeffrey A. Borgia¹  Imad A. M. Tarhoni¹  Stephen Szajek²  Fei Chu²  Mary Beth Madonna²  Nicholas J. Skertich² 

[1] Department of Pathology, Rush University Medical Center, Chicago, IL 60612, USA;Department of Surgery, Division of Pediatric Surgery, Rush University Medical Center, Chicago, IL 60612, USA;

关键词: neuroblastoma;    doxorubicin;    drug resistance;    programmed death ligand 1;    checkpoint protein molecules;    checkpoint molecule inhibition;   

DOI  :  10.3390/cancers14030751

来源: DOAJ

【 摘 要 】

Neuroblastoma is a common childhood cancer with poor prognosis when at its advanced stage. Checkpoint molecule inhibition is successful in treating multiple advanced adult cancers. We investigated PD-L1 and other checkpoint molecule expression to determine their roles in drug resistance and usefulness as targets for drug therapy. We developed three doxorubicin-resistant (DoxR) cell lines from parental cell lines. Matrigel in vitro invasion assays were used to compare invasiveness. Western blot assays were used to compare PD-L1 expression. Immuno-oncology checkpoint protein panels were used to compare concentrations of 17 checkpoint molecules both cellular and soluble. PD-L1 and 12 other checkpoint molecules were present in all cell lysates of each cell line without significantly different levels. Three were solubilized in the media of each cell line. PD-L1 is expressed in all DoxR and parental neuroblastoma cells and may be a potential target for drug therapy although its role in drug resistance remains unclear. Benchmarking checkpoint molecules provides the basis for future studies identifying targets for directed therapy and biomarkers for cancer detection or prognosis.

【 授权许可】

Unknown