Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors

Atsuko Kasajima, Yuichi Ishikawa, Ayaka Iwata, Katja Steiger, Naomi Oka, Hirotaka Ishida, Akira Sakurada, Hiroyoshi Suzuki, Toru Kameya, Björn Konukiewitz, Günter Klöppel, Yoshinori Okada, Hironobu Sasano, Wilko Weichert

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small-cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas). Data were correlated with clinicopathological factors and survival. Moderate or high tumor-associated inflammation was detected in 4 carcinoids (7%) and in 37 neuroendocrine carcinomas (20%). PD-L1 immunoreactivity was seen in immune cells of 73 (39%) neuroendocrine carcinomas, while tumor cells were labeled in 21 (11%) cases. Inflammatory cells and tumor cells in carcinoids lacked any PD-L1 expression. In neuroendocrine carcinomas, PD-L1 positivity in immune cells, but not in tumor cells, was associated with intratumoral CD8+ cell infiltration (P < 0.001), as well as with the severity of tumor-associated inflammation (P < 0.001). In neuroendocrine carcinomas, tumor-associated inflammation and PD-L1 positivity in immune cells correlated with prolonged survival and the latter factor was also an independent prognosticator (P < 0.01, hazard ratio 0.4 for overall survival, P < 0.001 hazard ratio 0.4 for disease-free survival).

Original languageEnglish
Pages (from-to)339-350
Number of pages12
JournalEndocrine-Related Cancer
Issue number3
Publication statusPublished - 2018 Mar


  • Inflammation
  • Neuroendocrine carcinoma
  • PD-L1
  • Prognosis
  • Pulmonary carcinoid


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