Gastrointestinal stromal tumors: Immune protein expression and clinical outcomes.

Abstract

124 Background: The immune microenvironment is emerging as an important prognostic factor with potential therapeutic targets for various malignancies. Although programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) have been studied in some tumor types, significance of their expression in gastrointestinal stromal tumors (GISTs) is largely unknown. Methods: Tissue microarrays at an academic tertiary care center were constructed from pathology files from 1996 to 2016. Immunohistochemistry for PD-L1 and IDO was performed and correlated with tumor size, mitoses, and clinical outcomes. Tumor infiltrating lymphocytes (TILs) were counted using image analysis software. Results: 131 GISTs were analyzed. Median patient age was 64 years (range 30-89); 51.1% were male. Tumor location included 89 stomach (67.9%), 34 small bowel (26.0%), 4 colorectal (3.1%), and 4 other (3.1%). Median follow-up was 58 months. Mean tumor size was 5.6±4.5cm, range 0.5 to 24; mean mitoses were 7.2/50HPF. 19 (14.5%) metastasized to mesentery (n = 8), liver (n = 6), and elsewhere (n = 5). Mean survival was 61 months (range 7-127); 5 patients died of disease (3.8%). PD-L1 immunostain was positive in 89 (67.9%), including 11 of 19 (57.9%) malignant and 78 of 112 (69.6%) benign tumors (p = 0.4). PD-L1 positive tumors were larger (6.3±4.4 vs. 4.4±3.4 cm; p = 0.02) and had more mitoses/50HPF (8.9±5.4 vs. 3.9±3.5; p = 0.006) than PD-L1 negative tumors. IDO immunostain was positive in 116 (88.5%), including 14 of 19 (73.7%) malignant and 102 of 112 (91.1%) benign tumors (p = 0.07). There was no significant difference in size or mitotic count between IDO positive and negative tumors. Mean number of CD8-positive TILs was 168±35/mm2 and mean number of PD-L1 positive TILs was 147±28/mm2 in PD-L1 positive tumors. PD-L1 positive tumors had significantly more TILs than PD-L1 negative tumors (113±21 vs. 104±18; p < 0.001). Conclusions: The majority of GISTs express PD-L1 and IDO. Expression of PD-L1 was associated with increased tumor size and higher mitotic activity. PD-L1 and IDO could play a significant role in the tumor biology of GISTs; immunotherapy targeting one or both may provide novel treatment options.