Abstract 1191: PD-L1 expression and the tumor immune microenvironment in NUT carcinoma

Abstract

Abstract Nuclear protein in testis (NUT) carcinoma is a rare, highly aggressive malignancy that is defined by translocations of the NUTM1 gene and has a median survival of less than one year. Although immunotherapy is an attractive novel therapeutic option, the immune microenvironment has not yet been characterized in this tumor type. We performed immunohistochemistry for PD-L1, IDO1, CD8, CD68, FOXP3 and myeloperoxidase on whole-slide sections from 9 cases of NUT carcinoma, quantified immune cell subsets using Halo image analysis software, manually scored percentage of PD-L1 and IDO1 expression in tumor cells, and classified immune cell PD-L1 expression as focal (≤5%) or non-focal (>5%). The 9 NUT carcinomas included 6 sinonasal, 2 mediastinal, and 1 soft tissue primaries. Median survival was 11 months (range 2-19); 7 patients (78%) died of disease while 2 (22%) had no evidence of disease at last follow up (12 and 19 months). All tumors demonstrated a dominant population of myeloperoxidase+ neutrophils, with a mean density of 954/mm2 (range 14-2311). There were also a mean 59/mm2 CD8+ cytotoxic T-cells (range 15-107), 75/mm2 FOXP3+ T-regulatory cells (range 9-349), and 54/mm2 CD68+ macrophages (range 0-417). Immune cell density did not correlate with survival. Four tumors (44%) expressed PD-L1, with mean 17% positivity (range 0-70%). PD-L1 expression was associated with improved survival (p=0.02), with higher mean PD-L1 levels in surviving patients (65% vs. 4%, p<0.001). Two tumors (22%) expressed non-focal PD-L1 on tumor-infiltrating lymphocytes, which was also associated with survival (100% vs. 0%, p=0.03); whereas all tumors showed non-focal PD-L1 on neutrophils and macrophages. PD-L1+ tumors also had more CD8+ T-cells per mm2 (81 vs 41, p=0.07). Three tumors (33%) expressed IDO1, which was associated with improved survival (p=0.01). Overall, NUT carcinoma demonstrates an immunosuppressive microenvironment with a dominant population of tumor-infiltrating neutrophils that also show PD-L1 expression. However, evidence of PD-L1 and IDO1 expression on tumor cells with associated cytotoxic T-cell response and improved prognosis suggests that adaptive immunity plays an important role in NUT carcinoma outcomes, raising the possibility that immunotherapy might be harnessed to augment this response. Note: This abstract was not presented at the meeting. Citation Format: Lisa M. Rooper, Nyall R. London, Janis M. Taube, William H. Westra, Justin A. Bishop, Hyunseok Kang. PD-L1 expression and the tumor immune microenvironment in NUT carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1191.