A Long-term Response to Nivolumab in a Case of PD-L1-negative Lung Adenocarcinoma with an EGFR Mutation and Surrounding PD-L1-positive Tumor-associated Macrophages

Intern Med. 2019 Oct 15;58(20):3033-3037. doi: 10.2169/internalmedicine.2875-19. Epub 2019 Jul 10.

Abstract

Anti-programmed cell death 1 (PD-1) antibodies have poor efficacy in epidermal growth factor receptor (EGFR)-mutated lung cancer. We herein report a 72-year-old man with programmed cell death-ligand 1 (PD-L1)-negative lung adenocarcinoma harboring an EGFR mutation that responded to nivolumab for more than 2 years. A pathological examination revealed infiltration of CD8-positive lymphocytes and macrophages expressing CD68, CD206, and PD-L1 into the PD-L1-negative tumor; CD206 expression is a marker of immunosuppressive tumor-associated macrophages (TAMs). The presence of PD-L1-positive TAMs in the tumor environment might be a predictor of a positive response to anti-PD-1 antibodies.

Keywords: EGFR mutations; lung adenocarcinoma; nivolumab; tumor-associated macrophages.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma of Lung / diagnosis
  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics
  • Aged
  • B7-H1 Antigen / metabolism*
  • Biopsy
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • ErbB Receptors / genetics
  • Humans
  • Lung / diagnostic imaging
  • Lung / metabolism
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Macrophages / pathology*
  • Male
  • Mutation*
  • Nivolumab / therapeutic use*
  • Tomography, X-Ray Computed

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • DNA, Neoplasm
  • Nivolumab
  • EGFR protein, human
  • ErbB Receptors