Programmed death ligand 1/indoleamine 2,3-dioxygenase 1 expression and tumor-infiltrating lymphocyte status in renal cell carcinoma with sarcomatoid changes and rhabdoid features

Abstract

Renal cell carcinoma (RCC) with sarcomatoid changes and rhabdoid features has shown poor outcomes. Several immune checkpoint inhibitors including programmed cell death protein 1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors have been approved for the treatment of RCC. Combination therapy using PD-1/PD-L1 and indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors has also been used to treat various malignancies. However, little is known about IDO1 expression and therapeutic effects of the IDO1 inhibitor in RCC. Herein, we retrospectively analyzed the expression of PD-L1/IDO1 and examined its relationship with tumor-infiltrating lymphocyte (TIL) status and prognostic effect. We investigated the PD-L1, IDO1, CD3+, CD4+, and CD8+ immunoexpression status in 60 cases of sarcomatoid/rhabdoid RCC. The PD-L1 and IDO1 results were defined by the tumor proportion score. For the evaluation of TIL status, we counted the number of lymphocytes located in the tumor and averaged the numbers over five high-power fields for each case. The results revealed PD-L1 and IDO1 expression was observed more frequently in the sarcomatoid/rhabdoid component than in the nonsarcomatoid/nonrhabdoid component. The correlation between PD-L1 and IDO1 expression was significant (P=0.0076). PD-L1 expression and coexpression of PD-L1 and IDO1 were correlated with a high density of CD3+, CD4+, and CD8+ T cells. There was no significant difference in overall survival among the patients with PD-L1 and/or IDO1 expression, but PD-L1 expression and coexpression were related to poor progression-free survival. Our results suggest that combination therapy using the PD-1/PD-L1 inhibitor and IDO1 inhibitor may be effective for treating sarcomatoid/rhabdoid RCC.