Deep immunophenotyping of natural killer T(NKT) cells in tumor microenviroment of heptatocellular carcinoma(HCC)

• Main Author: Subramaniam, Shaalini
• Other Authors: Thirumaran s/o Thanabalu
• Format: Final Year Project
• Language: English
• Published: 2016
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/67973
• Institution: Nanyang Technological University

The immune microenvironment plays an important role in tumor progression including in hepatocellular carcinoma (HCC). However, detailed understanding of immune subsets within the microenvironment, especially Natural Killer T cells (NKT) remains elusive. Using high throughput immunophenotyping tool: Time-Of-Flight Mass Cytometry (CyTOF), we identified unique NKT populations enriched in tumor versus peripheral circulation and non-tumor (NT). Firstly, tumor is enriched with CD8+iNKT cells that showed immunosuppressive phenotypes with the expression of PD-1, an exhaustion marker. They however remained functionally competent with the expression of IFN when activated ex vivo. Secondly, when compared to the NT compartment, CD4+iNKT cells were particularly enriched in tumor. Thirdly, the expression of IL22 by tumor-enriched iNKT cells when activated ex vivo may indicate a potential role for tumor progression. Furthermore, some NKT cells enriched in tumor expressed a homing receptor CXCR3 indicating their potential for tumor infiltration in response to CXCL10. Lastly, tumor microenvironment as analyzed at the gene expression level was geared towards functionally incompetent NKT cells. The current study improves our understanding of the phenotypes of NKT cells enriched in HCC and implicates potential intervention for cancer immunotherapy in future.