Adjuvant Chemotherapy Increases Programmed Death-Ligand 1 (PD-L1) Expression in Non-small Cell Lung Cancer Recurrence

Clin Lung Cancer. 2019 Sep;20(5):391-396. doi: 10.1016/j.cllc.2019.05.013. Epub 2019 Jun 5.

Abstract

Background: Despite recent studies, the effect of chemotherapy on programmed death-ligand 1 (PD-L1) expression remains controversial. In this study, we investigated whether PD-L1 expression is affected by platinum-based chemotherapy. Furthermore, we evaluated correlation of PD-L1 expression with oncogenic driver alterations.

Materials and methods: We retrospectively evaluated changes in PD-L1 expression by immunohistochemical (IHC) analysis in resected specimens and in biopsies at non-small cell lung cancer recurrence in patients receiving or not adjuvant chemotherapy after surgical resection. Four IHC score groups were defined: TC0 < 1%, T ≥ 1% and < 5%, TC2 ≥ 5% and < 50%, and TC3 ≥ 50%.

Results: Thirty-six patients with adenocarcinoma were included. Twenty (56%) patients underwent adjuvant chemotherapy, and 16 (44%) patients did not receive adjuvant chemotherapy. PD-L1 expression was present in 10 (28%) of 36 initial tumor specimens. From patients receiving adjuvant chemotherapy, 7 (35%) of 20 tumor biopsies showed significant upregulation in PD-L1 expression at recurrence. In contrast, from patients with no adjuvant therapy, only 2 (12.5%) of 16 showed a change in PD-L1 expression. Six (17%) of 36 patients were PD-L1-negative in the primary tumor and turned positive at recurrence. KRAS mutation was present in 70% of patients expressing PD-L1.

Conclusion: PD-L1 expression in non-small cell lung cancer can change from primary to recurrence, implicating the need for re-biopsy at recurrence. Moreover, chemotherapy might increase expression of PD-L1, supporting a combinatorial therapy with chemotherapy and anti-PD(L)1 treatment.

Keywords: Checkpoint inhibitors; Chemotherapy; Immunotherapy; Non-small cell lung cancer; PD-L1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Chemotherapy, Adjuvant / methods*
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Platinum Compounds / therapeutic use*
  • Retrospective Studies

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Platinum Compounds