PD-L1 Copy Number Variation Does Not Correlate With PD-L1 Expression or Response to Anti-PD-1 Immunotherapy In Patients With Advanced Melanomas

Appl Immunohistochem Mol Morphol. 2020 Feb;28(2):161-165. doi: 10.1097/PAI.0000000000000712.

Abstract

Predicting the response to PD-1/PD-L1 immune checkpoint blockade in patients with metastatic melanoma remains challenging. In this study, we have investigated for the relationships between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. We studied the formalin-fixed paraffin-embedded tumor samples of 36 patients with metastatic melanoma using PD-L1 immunohistochemistry (IHC) and PD-L1/chromosome 9 fluorescent in situ hybridization (FISH). PD-L1 IHC was positive in 3 patients (8.33%, with >5% stained tumor cells) and PD-L1 FISH test revealed 5 (13.8%) PD-L1 amplifications, 8 (22.2%) PD-L1 gains, and 2 (5.5%) PD-L1 losses. Among 14 responders and 13 nonresponders to anti-PD-1 immunotherapy, we concluded that there was no significant relationship between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. In our study, the determination of PD-L1 expression using IHC and PD-L1 copy number using FISH was insufficient to predict the response to PD-1/PD-L1 immune checkpoint blockade in patients with advanced melanomas.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • B7-H1 Antigen* / biosynthesis
  • B7-H1 Antigen* / genetics
  • Female
  • Gene Dosage*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunotherapy*
  • Male
  • Melanoma* / genetics
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • Melanoma* / therapy
  • Neoplasm Metastasis
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / biosynthesis
  • Neoplasm Proteins* / genetics
  • Nivolumab
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor* / genetics
  • Programmed Cell Death 1 Receptor* / metabolism
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology
  • Skin Neoplasms* / therapy

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab