Promotie Z. (Zhouhong) Ge

Liver cancers was the sixth most commonly diagnosed cancer type and the fourth leading cause of cancer related death worldwide in 2018. Hepatocellular carcinoma (HCC) comprises 75%-85% of all liver cancer cases. More than 80% of HCC patients are diagnosed at advanced stage and their median survival is less than 2 years. Both the current diagnosis and treatments of advanced HCC remain to be improved. 

In this thesis we aim to optimize existing immunotherapy for HCC with a strong emphasis on checkpoint inhibition. PD-1 blockade is clinically effective in about 20% of advanced HCC patients. We demonstrated that co-blockade of TIGIT and PD-1 improved CD8+ tumor-infiltrating T cells (TILs) cytotoxicity. Therefore co-blocking TIGIT and PD-1 could be a promising immune therapeutic strategy for HCC patients.

Additionally, we aim to identify tumor antigens that can be tumor-specific targets for immunotherapy. Boosting tumor-specific T-cell responses with for instance vaccination-strategies may be part of a combination with immune checkpoint inhibitors to form a superior immunotherapeutic approach. We established a panel of 12 testis-restricted cancer testis antigens (CTAs) expressed in tumors of most HCC-patients. CTAs can be expressed in tumor-free liver and might be indicative for post-resection HCC-recurrence and survival. 
Lastly, we aim to detect tumor-associated mutations in paired circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in HCC patients. We found that oncogenic mutations could be detected in ctDNA from advanced HCC patients and predicts prognosis. ctDNA analysis of liquid biopsies appears promising for identifying druggable mutations.

Due to corona, the PhD defences do not take place publicly in the usual way in the Senate Hall or in the Professor Andries Querido Room. The candidates will defend their dissertation either in a small group or online.