• Kazuki Takada, Kenichi Kohashi, Mototsugu Shimokawa, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Takashi Seto, Yoshinao Oda, and Yoshihiko Maehara.
• 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.
• Lung Cancer. 2019 Feb 1; 128: 26-32.

ObjectivesCombination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC).Materials And MethodsThe expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry.ResultsAmong 202 patients, 176 (87.1%) were positive for IDO1 expression, 106 (52.5%) were positive for PD-L1 expression, and 99 (49.0%) showed co-expression of IDO1/PD-L1 proteins. Fisher's exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P =  0.0011). Kaplan-Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P =  0.0122, P =  0.0303 and P =  0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student's t-test: P =  0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher's exact test: P =  0.0033, P =  0.0003, and P <  0.0001, respectively).ConclusionsIDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.Copyright © 2018 Elsevier B.V. All rights reserved.

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