PD-L1 expression and CD8+ tumor-infiltrating lymphocytes are associated with ALK rearrangement and clinicopathological features in inflammatory myofibroblastic tumors.Oncotarget 2017; 8(52):89465-89474O
Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that are composed of myofibroblastic cells accompanied by inflammatory infiltrate. We investigated the immune profiles of IMTs, including PD-L1 expression and proportion of CD8+ tumor-infiltrating lymphocytes (TILs), as well as its clinicopathological characteristics according to ALK gene rearrangementstatus.
Twenty-eight IMTs from 25 patients were retrieved from our pathology files (2005-2015), and their clinicopathological parameters and outcomes were analyzed. Immunohistochemistry (IHC) was performed using whole-tissue sections to detect PD-L1 and CD8 expression, and fluorescent in situ hybridization (FISH) analysis and IHC were performed using tissue microarrays to identify rearrangements in the ALK, ROS1, and RET genes.
ALK rearrangement was observed in 11 cases (44.0%), and all cases exhibited diffuse cytoplasmic ALK expression during IHC. ROS1 or RET rearrangement was not detected using IHC or FISH. IMTs harboring ALK rearrangement (ALK-positive) were located in the lungs (n = 7), genitourinary tract (n = 2), and mesentery (n = 1). The mean patient age was 33.2 years for ALK-positive IMTs and 53.1 years for ALK-negative IMTs. All patients with ALK-positive IMTs survived without recurrence or metastasis. IMTs with metastasis and/or recurrence were ALK-negative and exhibited elevated PD-L1 expression (positive tumor cells: 70.0% vs. 21.3%, P = 0.023; H-score: 107.5 vs. 26.3, P = 0.005). In addition, ALK-negative IMTs had a more CD8+ TILs, compared to ALK-positive IMTs (23.3% vs. 8.9%, P = 0.027).
ALK-positive IMTs are characterized by younger age, well-defined margins, frequent involvement of the lung, and fewer CD8+ TILs. Greater PD-L1 expression was observed in IMTs with tumor necrosis and metastasis/recurrence, which were also negative for ALK rearrangement. These results suggest that immune checkpoint inhibitors may be a novel option for treating patients with advanced IMT.