Kazuki Takada1, Kenichi Kohashi2, Mototsugu Shimokawa3, Akira Haro4, Atsushi Osoegawa4, Tetsuzo Tagawa4, Takashi Seto5, Yoshinao Oda2, Yoshihiko Maehara6. 1. 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. 2. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 3. Clinical Research Institute, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan. 4. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 5. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan. 6. Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-ku, Fukuoka, 815-8588, Japan.
Abstract
OBJECTIVES: Combination 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 METHODS: The 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. RESULTS: Among 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). CONCLUSIONS: IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.
OBJECTIVES: Combination 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 NSCLCpatients. 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 METHODS: The 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. RESULTS: Among 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). CONCLUSIONS:IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.
Authors: Lin Cheng; Bangbi Weng; Changsheng Jia; Lin Zhang; Bin Hu; Li Deng; Nan Mou; Fengjun Sun; Jing Hu Journal: Front Pharmacol Date: 2022-08-19 Impact factor: 5.988
Authors: Stephanie Tuminello; Daniel Sikavi; Rajwanth Veluswamy; Cesar Gamarra; Wil Lieberman-Cribbin; Raja Flores; Emanuela Taioli Journal: Transl Lung Cancer Res Date: 2020-08