Yuka Kozuma1, Kazuki Takada2, Gouji Toyokawa1, Kenichi Kohashi3, Mototsugu Shimokawa4, Fumihiko Hirai1, Tetsuzo Tagawa1, Tatsuro Okamoto1, Yoshinao Oda3, Yoshihiko Maehara1. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: k_takada@surg2.med.kyushu-u.ac.jp. 3. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. 4. Clinical Research Institute, National Kyusyu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.
Abstract
BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. MATERIALS AND METHODS: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. RESULTS: IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that ≥1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β. CONCLUSION: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.
BACKGROUND:Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. MATERIALS AND METHODS: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. RESULTS:IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that ≥1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β. CONCLUSION: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.
Authors: Tao Fan; Yu Liu; Hengchang Liu; Liyu Wang; He Tian; Yujia Zheng; Bo Zheng; Liyan Xue; Chunxiang Li; Jie He Journal: Front Oncol Date: 2022-03-22 Impact factor: 6.244
Authors: Matthew D Hellmann; Scott Gettinger; Laura Q M Chow; Michael Gordon; Mark M Awad; Edward Cha; Xiaohua Gong; Gongfu Zhou; Chris Walker; Lance Leopold; Rebecca S Heist Journal: Int J Cancer Date: 2020-03-20 Impact factor: 7.396