PD-L2 Expression as a Potential Predictive Biomarker for the Response to Anti-PD-1 Drugs in Patients with Non-small Cell Lung Cancer

Anticancer Res. 2018 Oct;38(10):5897-5901. doi: 10.21873/anticanres.12933.

Abstract

Background/aim: To investigate the role of programmed cell death-ligand 2 (PD-L2) expression as a predictive biomarker for response to anti-programmed cell death-1 (PD-1) drugs in patients with non-small cell lung cancer (NSCLC).

Patients and methods: Ten patients who had undergone curative lung resection and received the anti-PD-1 drugs for the recurrence were enrolled. The cut-off value for PD-L2 (antibody clone 176611) expression on tumor cells was set at 50%. Tumor response was evaluated according to immune-related response criteria.

Results: Seven patients (70.0%) were positive for PD-L2. The response rates were 28.6% (2/7) and 33.3% (1/3) in patients with PD-L2-positive and PD-L2-negative NSCLC, respectively. Disease control was obtained in 2 patients despite the programmed cell death-ligand 1 (PD-L1)-negativity (antibody clone 22C3: 0%, antibody clone SP142: 0%), and these tumors expressed PD-L2 (≥1%).

Conclusion: PD-L2 expression may be a target of immunotherapy in patients with PD-L1-negative NSCLC.

Keywords: Programmed cell death-ligand 1; non-small cell lung cancer; programmed cell death-ligand 2.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary*
  • Bone Neoplasms / surgery
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Retrospective Studies
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor