Abstract

Programmed death-ligand 1 (PD-L1) is an inhibitory transmembrane protein that can prevent autoimmune response. Upregulated PD-L1 serves as a predictive biomarker for patients who may respond well to immune checkpoint therapies. However, variable associations of PD-L1 level with prognoses have been report ed. In t hi s st udy, a short pept i de sequence corresponding to PD-L1 amino acids 172-187 (from the extracellular Ig-like C-type domain, and with high predicted antigenicity and hydrophilicity) was used to generate a monoclonal antibody (mAb). The resultant PD-L1 mAb, clone HC16, was examined for binding specificity and reactivity in cancer cell-lines, as assessed by immunocytochemical, immunoblotting, and co-immunoprecipitation. The potential diagnostic and clinical applicability of clone HC16 was further tested using malignant tissue arrays derived from various cancer t ypes anal yzed wi t h an aut omat ed i mmunohi st ochemi cal (I HC) st ai ni ng pl at f or m. Additionally, tumor samples from patients diagnosed with non-small cell lung cancer (NSCLC) were analyzed by western blotting. Clone HC16 showed obvious staining activity in lung and breast cancer tissues. Int erest i ngl y, we observed t hat PD-L1 l evel was negatively associated with clinical stage in NSCLC. Strong PD-L1 expression tended to be found in patients diagnosed with bronchioloalveolar carcinoma (BAC). These results demonstrate that clone HC16 harbors good target specificity and is suitable for further development in diagnostic tools to assess PD-L1 expression in human tissues. In addition, our findings also suggest a role for PD-L1 in a non-invasive subtype of lung cancer.

Original languageEnglish
Pages (from-to)77-89
Number of pages13
JournalHistology and Histopathology
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Monoclonal antibody
  • Non-small cell lung cancer (NSCLC)
  • Programmed death-ligand 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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