Abstract 2341: Indoleamine 2,3 dioxegenase 1 (IDO1) and T-cell infiltration in esophageal cancer

Abstract

Abstract Background: Immune checkpoint blockade is emerging as an important immunotherapeutic strategy in esophageal cancer, yet response rates remain low. IDO1 is a rate-limiting immunosuppressive enzyme that may contribute to resistance to immune checkpoint blockade in human cancer, and may be an important immunotherapeutic target. The expression pattern of IDO1 across esophageal cancer histologies remains poorly understood. Here, we utilize immunohistochemistry to characterize the expression pattern and relevance of IDO1 in esophageal cancer. Methods: Tumor microarray containing samples of surgically resected esophageal carcinoma and normal esophageal tissue were stained for IDO1 and CD3ϵ (marker of T-cell infiltration). Demographic and staging data were collected. Light microscopic immunoscoring analysis was performed. Correlations were analyzed using Fisher’s exact test. Results: 192 samples were assessed (180 esophageal carcinoma, 12 normal esophageal tissue.) Median age was 60 years (range 34-78). 69.3% of patients were male. Of the 180 esophageal carcinoma samples, 150 (83.3%) squamous cell carcinoma, 16 (8.9%) adenocarcinoma, 13 (7.2%) small cell carcinoma, 7 (3.9%) undifferentiated carcinoma, 2 (1.1%) carcinoid, 2 (1.1%) adenosquamous carcinoma, and 2 (1.1%) adenoid cystic carcinoma. IDO1 was positive in 81 samples (45.0%) overall with 52.0% in squamous cell carcinoma and 46.7% in adenocarcinoma. Positive IDO1 was associated with higher stage and nodal positivity (P=0.04). T-cell infiltration in esophageal carcinoma specimens was present in 133 samples (73.9%). IDO1 positivity correlated with increased T-cell infiltration (P<0.01). Conclusions: Here our study suggests that expression of IDO1 is positive in almost half of esophageal tumors, and is associated with T-cell infiltration. Additionally, positive IDO1 was associated with higher likelihood of nodal involvement and more advanced stage. These data suggest that IDO1 may play a role in adaptive immune resistance in T-cell inflamed tumors, and that incorporating IDO1 inhibition into an immunotherapeutic strategy in esophageal cancer may enhance T-cell mediated anti-tumor effect. Citation Format: Ari J. Rosenberg, Derek A. Wainwright, Angela J. Fought, Lijie Zhai, Kristen Lauing, Victoria M. Villaflor. Indoleamine 2,3 dioxegenase 1 (IDO1) and T-cell infiltration in esophageal cancer [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 2341.