PD-L1 and IDO-1 expression in undifferentiated pleomorphic sarcoma: The associations with tumor infiltrating lymphocytes, dMMR and HLA class I

Abstract

The prognosis of undifferentiated pleomorphic sarcoma (UPS) is generally unfavorable. Recently, clinical trials such as SARC028 demonstrated the utility of cancer immunotherapy for soft tissue sarcomas. The aim of the present study was to assess the expression of PD-L1 and IDO-1 as prognostic factors and therapeutic targets. A total of 52 primary UPS cases were retrieved and two UPS cell lines were utilized for supplementary analysis. Immunohistochemical staining of anti-PD-L1 (28-8), IDO-1, CD8, CD4, CD3, HLA class I, MSH2, MSH6, MLH1 and PMS2 was carried out. Immunohistochemically, 19 of 52 (36.5%) cases showed PD-L1 expression at least focally (≥1%) and 5 of 52 (9.62%) showed strong PD-L1 expression (≥50%). Overall, 25 of 52 (48.1%) cases expressed IDO-1 (≥1%). Two tumors were evaluated as having deficient mismatch repair and six tumors as having the loss of HLA class I. PD-L1 expression (≥1%) was significantly related to the infiltration of CD8- and CD3-positive lympho- cytes, but strong PD-L1 expression (≥50%) did not present a significant relationship with tumor-infiltrating lymphocytes. IDO-1 expression was also associated with CD8-, CD4-, and CD3-positive lymphocytes. In vitro, both PD-L1 and IDO-1 were induced by IFN-γ stimulation. In survival analysis, strong PD-L1 expression (≥50%) was a significant poor prognostic factor, while IDO-1 expression (≥1%) was a favorable one. In conclusion, UPS was shown to frequently express PD-L1 and IDO-1. It was suggested that PD-L1 expression (≥50%) and IDO-1 expression are poor and favorable prognostic factors of UPS patients, respectively.