J Cancer 2019; 10(1):267-276. doi:10.7150/jca.27507 This issue

Research Paper

High Expression of Indoleamine 2, 3-Dioxygenase in Adenosquamous Lung Carcinoma Correlates with Favorable Patient Outcome

Wenjuan Ma1*, Hao Duan1*, Rongxin Zhang1*, Xing Wang2, Haineng Xu3, Qianghua Zhou1, Li Zhang1✉

1. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
2. Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
3. Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, 19104, USA
*These authors contributed equally to this work.

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Ma W, Duan H, Zhang R, Wang X, Xu H, Zhou Q, Zhang L. High Expression of Indoleamine 2, 3-Dioxygenase in Adenosquamous Lung Carcinoma Correlates with Favorable Patient Outcome. J Cancer 2019; 10(1):267-276. doi:10.7150/jca.27507. Available from https://www.jcancer.org/v10p0267.htm

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Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan (Trp) metabolism, is generally considered to be an immunosuppressive molecule. The prognostic role of IDO expression in tumor has not been well studied in non-small cell lung cancer (NSCLC) and even not been reported in adenosquamous lung carcinoma (AdSqLC). Herein, the aim of this study is to investigate the prognostic significance of IDO expression in patients with AdSqLC.

Patients and Methods: We conducted immunohistochemical analyses of IDO expression, as well as CD3 and CD8 expression, in 183 primary tumor tissue samples from patients with AdSqLC treated at our institution between July 1999 and September 2014. Patients' clinicopathological characteristics were retrospectively reviewed. Survival analysis was performed in the entire cohort of patients and those who received radical resection, respectively.

Results: IDO was expressed in 146 (79.8%) tumor samples. A higher level of IDO expression was significantly associated with increased CD8+ tumor-infiltrating lymphocytes (TILs) in tumor tissues (P<0.001). Surprisingly, overall survival (OS) was significantly better for patients with high IDO expression (hazard ratio (HR)= 0.505; confidence interval (CI)= 0.329-0.775; P=0.002) for the entire cohort. In patients who were unable to be treated with radical resection, IDO expression had no effect on OS (P=0.598). In contrast, a significant, independent association between high expression of IDO and better OS (HR=0.469; CI=0.290-0.758; P=0.002) was identified in patients who received radical resection.

Conclusions: IDO is expressed in most AdSqLC tissues, with a higher level of IDO expression associated with an occurrence of CD8+ TILs. Moreover, IDO expression in tumor promises to serve as a strongly independent favorable prognostic factor, particularly in patients who received radical resection.

Keywords: Indoleamine 2, 3-dioxygenase, lung cancer, radical resection, prognosis