PD-L1 is Fascinating but IDO Needs Attention in Non-HCV and Non-HBV-Associated Hepatocellular Carcinoma Patients

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer that is modulated by the immune system. Programmed cell death ligand-1 (PD-L1) has emerged as a novel therapeutic target in various cancers. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is associated with poor prognoses in various cancer types. The aim of this study was to investigate the PD-L1 expression, and clinicopathological features of non-HCV and non-HBV-associated HCC patients, including IDO expression. PATIENTS AND METHODS: In this study, immunohistochemical analysis was performed to analyze the expression of PD-L1 and IDO. Formalin-fixed paraffin-embedded HCC tumor tissues (n=50) were obtained from the pathology department, at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan between 2005 and 2022. All the patients were HBV and HCV negative. Furthermore, it was a rare group of patients with no previous history of any viral hepatitis. In addition, for categorical and continuous variables chi-square or Fisher exact test and Mann–Whitney U-test was performed. RESULTS: Of 50 tissue specimens, PD-L1+ was observed in 21 [high: 12 (24%), low: 9 (18%)] and PD-L1- was observed in 29 HCC patients. IDO+ was observed in all 50 specimens [high: 42 (84%), low: 8 (16%)]. Additionally, both PD-L1 and IDO had high expression in 11 (22%) patients. While both PD-L1 and IDO had low expression in 2 (4%) patients. Furthermore, in IDO+/PD-L1- group, 20 (69%) out of 29 patients died while in the IDO+/PD-L1+ group, 9 (43%) out of 21 patients died. CONCLUSION: Evaluation of IDO and PD-L1 expression may add therapeutic advantage in non-HCV and non-HBV-associated HCC patients that overexpress IDO. Further validation in a larger cohort is warranted.