Heterogeneity of Response and Immune System Activity during Treatment with Nivolumab in Hepatocellular Carcinoma: Results from a Single-Institution Retrospective Analysis

• Main Authors: Ilario Giovanni Rapposelli, Serena De Matteis, Paola Lanuti, Martina Valgiusti, Giulia Bartolini, Paola Ulivi, Giorgia Marisi, Federica Pedica, Valentina Burgio, Giovanni Luca Frassineti, Stefano Cascinu, Andrea Casadei-Gardini
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Cancers
• Subjects: hepatocellular carcinoma; immunotherapy; pattern of response; peripheral blood mononuclear cells
• Online Access: https://www.mdpi.com/2072-6694/13/2/213

Treatment of hepatocellular carcinoma (HCC) is rapidly evolving, with many new therapeutic options; in particular, immunotherapy (IT) is acquiring a major role, even in combination regimens. Despite these promising results, an important limitation is the lack of prognostic and predictive factors that prevent provision of a tool for patient stratification in order to select the most appropriate strategy. Furthermore, response assessment can be challenging with IT due to peculiar patterns such as mixed responses or pseudoprogression. We analyzed biological and clinical features from the first 10 HCC patients treated with nivolumab in our institution. Analysis of patterns of response in CT assessment revealed complete response in pulmonary lesions, along with heterogeneous behavior in the liver and other organ lesions. Peripheral blood mononuclear cells (PBMC) analysis in the first four patients showed unique alterations in a patient with poor prognosis, both at baseline (lower percentage of effector T cells, higher percentage of natural killer T [NK/T] cells) and during treatment with nivolumab (decrease in nonclassical monocytes, increase in monocytic myeloid-derived suppressor cells [MO-MDSC]), suggesting a possible prognostic role for these features. Although obtained in a small cohort of patients, our results open a new perspective for understanding mechanisms underlying IT outcomes in HCC patients.