Indoleamine-2, 3-Dioxygenase in Non–Small Cell Lung Cancer: A Targetable Mechanism of Immune Resistance Frequently Coexpressed With PD-L1. (September 2018)

• Record Type: Journal Article
• Authors: Volaric, Ashley; Gentzler, Ryan; Hall, Richard; Mehaffey, James H.; Stelow, Edward B.; Bullock, Timothy N.; Martin, Linda W.; Mills, Anne M.
• Is Part Of: American journal of surgical pathology. Volume 42:Number 9(2018)
• Publication Date: 2018-09
• Subjects: IDO -- IDO-1 -- indoleamine-2, 3-dioxygenase -- non–small cell lung carcinoma -- NSCLC -- lung cancer -- immunotherapy -- PD-L1; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001099
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : The immune regulatory enzyme indoleamine-2, 3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non–small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown. One hundred two cases of NSCLC (51 adenocarcinomas, 9 adenosquamous carcinomas, and 42 squamous cell carcinomas) were evaluated for IDO-1 and PD-L1 expression by immunohistochemistry. IDO-1 expression was identified in 43% of NSCLC (42% of adenocarcinomas, 44% of adenosquamous carcinomas, and 43% of squamous cell carcinomas). Coexpression with PD-L1 (≥1%) was common (27% overall; 27% of adenocarcinomas, 33% of adenosquamous carcinomas, and 26% of squamous cell carcinomas). A smaller population of tumors showed isolated PD-L1 (25% overall; 16% of adenocarcinomas, 44% of adenosquamous carcinomas, and 33% of squamous cell carcinomas) or IDO-1 expression (15% overall; 14% of adenocarcinomas, 11% of adenosquamous carcinomas, and 17% of squamous cell carcinomas). In summary, IDO-1 is commonly expressed by NSCLC, and its frequent coexpression with PD-L1 may account for the increased efficacy seen with dual blockade of PD-1/PD-L1 and IDO in clinical studies. IDO-1 immunohistochemistry may be a useful biomarker for selection of patients who could benefit from dual-agent therapy and should be evaluated in prospective clinical trials using PD-1/PD-L1 and IDO inhibitors.