Departments of Pathology.
Internal Medicine, Division of Hematology/Oncology, University of Virginia, Charlottesville, VA.
Am J Surg Pathol. 2018 Sep;42(9):1216-1223. doi: 10.1097/PAS.0000000000001099.
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.
免疫调节酶吲哚胺 2,3-双加氧酶（IDO-1）抑制 T 细胞反应，并可能降低针对免疫检查点（如程序性死亡受体-1/程序性死亡配体-1（PD-1/PD-L1）的治疗方法的疗效。将 IDO-1 与 PD-1/PD-L1 抑制剂联合用于早期临床试验在非小细胞肺癌（NSCLCs）中显示出了一定的前景。然而，IDO-1 和 PD-L1 的共表达尚未得到充分研究，IDO-1 免疫组化表达作为治疗生物标志物的潜力尚不清楚。对 102 例 NSCLC（51 例腺癌、9 例腺鳞癌和 42 例鳞状细胞癌）进行了 IDO-1 和 PD-L1 表达的免疫组化评估。在 NSCLC 中发现 43%（42%的腺癌、44%的腺鳞癌和 43%的鳞状细胞癌）表达 IDO-1。与 PD-L1（≥1%）共表达很常见（总体 27%；27%的腺癌、33%的腺鳞癌和 26%的鳞状细胞癌）。一小部分肿瘤表现为孤立的 PD-L1（总体 25%；16%的腺癌、44%的腺鳞癌和 33%的鳞状细胞癌）或 IDO-1 表达（总体 15%；14%的腺癌、11%的腺鳞癌和 17%的鳞状细胞癌）。总之，IDO-1 在 NSCLC 中表达普遍，其与 PD-L1 的频繁共表达可能解释了在临床研究中观察到的双重阻断 PD-1/PD-L1 和 IDO 增加疗效的原因。IDO-1 免疫组化可能是选择可能受益于双重治疗的患者的有用生物标志物，应在使用 PD-1/PD-L1 和 IDO 抑制剂的前瞻性临床试验中进行评估。
