The immune profiling of tumour microenvironment upon Y-90 treatment in HCC patients

• Main Author: Lee, Yun Hua
• Other Authors: Chew Valerie
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/70823
• Institution: Nanyang Technological University

Yttrium-90 (Y-90) radioembolization serves as an important therapy for hepatocellular carcinoma (HCC) patients to downsize tumours and delay disease progression. However, its immunological impact on the tumour micronenvironment requires further understanding to improve its clinical efficacy. This study aims to investigate the immunological differences of tumours between treatment-naive patients and those who responded to Y-90 radioembolization using time-of-flight mass cytometry (CyTOF) and analysis of their gene expression profiles with next-generation sequencing (NGS). Our results showed a significantly stronger immune response in post-Y-90 patients. An enhanced expression of HLA-DR (MHC-II) on antigen-presenting cells (APCs), along with enrichment of tumour-infiltrating lymphocytes (TILs), particularly CXCR3+ CD4 and CD8 T cells, and T cell activation with enhanced Tim-3 and granzyme B expression were observed within the tumour microenvironment. Natural killer (NK) and natural killer T (NKT) cells of innate immunity were also significantly enriched and exhibited anti-tumour characteristics. Further NGS analysis supported our CyTOF data and further demonstrated increased expression of genes for antigen-presentation, T cell activation and innate immunity. These findings support the immuno-monitoring effect of Y-90 radioembolization and its potential in combinational immunotherapy for HCC.