PD-L1 induction by cancer-associated fibroblast-derived factors in lung adenocarcinoma cells

Chihiro Inoue, Yasuhiro Miki, Ryoko Saito, Shuko Hata, Jiro Abe, Ikuro Sato, Yoshinori Okada, Hironobu Sasano

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36 Citations (Scopus)


Cancer-associated fibroblasts (CAFs) exert various effects upon biological behaviours of cancer. In this study, we examined the correlation of CAFs with the intra-tumoural immune system in the lung adenocarcinoma microenvironment. We studied 27 and 113 cases of lung adenocarcinoma tentatively as Cohorts 1 and 2, respectively. The patients in Cohort 1 received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrent lung adenocarcinoma. α-smooth muscle actin (α-SMA), a surrogate marker for CAFs, was examined by immunohistochemistry. We then examined the effects of CAFs isolated from lung cancer tissues on programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma cell lines. No significant associations were detected between α-SMA status and the ratios of CD8/CD4 and Foxp3/CD8 in Cohort 1. However, α-SMA status was significantly associated with PD-L1 status in both Cohorts 1 and 2. Conditioned medium of CAFs significantly induced PD-L1 expression in lung adenocarcinoma cell lines, A549, PC-9, and H1975. Among the cytokines examined by antibody array, C-X-C motif chemokine ligand 2 (CXCL2) increased PD-L1 mRNA expression in these cell lines. CXCL2 is therefore considered to have a potential to induce PD-L1 expression in lung adenocarcinoma cells as a result of an interaction between carcinoma cells and CAFs. These findings did firstly demonstrate that CAFs indirectly influenced tumour immunity through increasing PD-L1 expression in lung adenocarcinoma cells.

Original languageEnglish
Article number1257
Issue number9
Publication statusPublished - 2019 Sept


  • Cancer associated fibroblasts
  • Lung adenocarcinoma
  • Programmed death ligand 1
  • Tumor microenvironment
  • α-smooth muscle actin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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