Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

J Cancer Res Clin Oncol. 2018 Jul;144(7):1219-1226. doi: 10.1007/s00432-018-2642-4. Epub 2018 Apr 19.

Abstract

Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer.

Materials and methods: We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy.

Results: PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin-gemcitabine combination (p = 0.020), while in the carboplatin-paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy.

Conclusions: This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.

Keywords: Chemotherapy; Immunohistochemistry; Lung cancer; PD-1; PD-L1.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / immunology
  • Biopsy
  • Bronchoscopy
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Humans
  • Immunohistochemistry
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Paclitaxel / administration & dosage
  • Programmed Cell Death 1 Receptor / biosynthesis
  • Programmed Cell Death 1 Receptor / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Deoxycytidine
  • Carboplatin
  • Paclitaxel
  • Cisplatin
  • Gemcitabine