Associate Professor Liu Haiyan

Research Interest

Mechanism of tumour promoting inflammation in the tumor microenvironment

The interactions between the tumor cells and the immune cells, as well as immune mediators play important roles in the development and metastasis of tumour. Therefore, understanding the immune suppressive mechanism in the tumour microenvironment provides targets for cancer immunotherapy. Using hepatocellular carcinoma (HCC) model, our laboratory identified several inflammatory cytokines that exert suppressive effects on the anti-tumour immune response. We are interested in further elucidating their regulatory roles in modulating immune cell functions as well as confirming their therapeutic potentials. We are also interested in the functions of innate immune cell subsets, including ILCs, NK cells and γδT cells, and their therapeutic potential for cancer immunotherapy.

Novel immunotherapeutic strategies in cancer vaccine and adoptive immunotherapy

Recent development in epitope prediction algorithm has made personalized cancer vaccine a reality in high mutation burden tumors. We plan to explore this immunotherapy strategy in a type of low mutation burden cancer such as AML combined with checkpoint blockade therapy in a form of RNA vaccine. We hypothesize that personalized cancer vaccine, coupled with immune-checkpoint inhibitors delivered in the form of RNA, can be an effective treatment option for AML patients. We will combine the approaches of computing algorithm prediction, T cell activation screening, linker sequence and adaptor protein design, and proof-of-concept validation with both murine leukemia models and patient PBMCs. We plan to establish screening platforms and provide preclinical evidence in translating personalized RNA-based cancer vaccine, combined with immune checkpoint blockade, to the clinical setting as our long-term objective. The success of Chimeric Antigen Receptor T Cell (CAR-T) therapy in solid tumors has been modest, which could be due to the immune-suppressive tumor microenvironment. We are developing strategies to optimize CAR-T therapy for solid tumors to overcome immune suppressions in the tumor microenvironment.

Awards

NUSMed Fortitude Award 2021

Society membership

Singapore Society of Immunology (Vice President)

Recent Publications

1. Huey Yee Teo, Yuan Song, Kylie Su Mei Yong, Yonghao Liu, Yu Mei, Zuhairah Binte Hanafi, Ying Zhu, Yen Leong Chua, Nicholas R. J. Gascoigne, Qingfeng Chen, Haiyan Liu (2023) IL12/18/21 pre-activation enhances the anti-tumor efficacy of expanded γδT cells and overcomes resistance to anti-PD-L1 treatment. Cancer Immunology Research 11 (7): 978–999.
2. Dandan Lin, Yu Mei, Lei Lei, Zuhairah Binte Hanafi, Ziqi Jin, Yonghao Liu, Yuan Song, Yinsheng Zhang, Bo Hu, Chunliang Liu, Jinhua Lu, Haiyan Liu (2022) Immune suppressive function of IL-1α release in the tumor microenvironment regulated by calpain 1. OncoImmunology 11(1): 2088467
3. Huanle Gong, Shoubao Ma, Jia Chen, Bingyu Yang, Shuangzhu Liu, Xin Liu, Jingjing Han, Xiaojin Wu, Lei Lei, Zhinan Yin, Hongjian Sun, Di Yu, Haiyan Liu (co-corresponding author), Depei Wu, Yang Xu (2022) Dendritic cell-derived IL-27 p28 regulates T cell program in pathogenicity and alleviates acute graft-versus-host disease. Signal Transduction and Targeted Therapy 7, 319
4. Hao Chang, Sharon WT Chew, Mengjia Zheng, Daniel CS Lio, Christian Wiraja, Yu Mei, Xiaoyu Ning, Mingyue Cui, Aung Than, Peng Shi, Dongan Wang, Kanyi Pu, Peng Chen, Haiyan Liu, Chenjie Xu (2021) Cryomicroneedles for transdermal cell delivery. Nature Biomedical Engineering 5, 1008–1018
5. Yonghao Liu, Yuan Song, Dandan Lin, Lei Lei, Yu Mei, Ziqi Jin, Huanle Gong, Ying Zhu, Bo Hu, Yinsheng Zhang, Lixiang Zhao, Huey Yee Teo, Ju Qiu, Wen Jiang, Chen Dong, Depei Wu, Yuhui Huang, Haiyan Liu (2019) NCR– group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development. EBioMedicine 41:333-344
6. Ziqi Jin, Lei Lei, Dandan Lin, Yonghao Liu, Yuan Song, Huanle Gong, Ying Zhu, Yu Mei, Bo Hu, Yan Wu, Guangbo Zhang, Haiyan Liu (2018) IL-33 released in the liver inhibits tumor growth via promoting CD4+ and CD8+ T cell responses in hepatocellular carcinoma. The Journal of Immunology 201(12):3770-3779
7. Yu Mei, Lixiang Zhao, Yonghao Liu, Huanle Gong, Yuan Song, Lei Lei, Ying Zhu, Ziqi Jin, Shoubao Ma, Bo Hu, Qing Sun, and Haiyan Liu (2017) Tumor vaccine combining AIDA-1 autotransporter and DNA vaccine element delivered by attenuated Salmonella to activate both tumor-specific CD4+ and CD8+ T cell responses. Cancer Immunology Research 5(6):503-514
8. Dandan Lin, Lei Lei, Yonghao Liu, Yinsheng Zhang, Bo Hu, Guangming Bao, Yuan Song, Ziqi Jin, Chunliang Liu, Yu Mei, Dedy Sandikin, Yan Wu, Lixiang Zhao, Xiao Yu, and Haiyan Liu (2016) Membrane IL-1α inhibits the development of hepatocellular carcinoma via promoting T and NK cell activation. Cancer Research 76(11):3179-88
9. Yuejun Liu, Yan Wu, Ying Wang, Yifeng Cai, Bo Hu, Guangming Bao, Hongying Fang, Lixiang Zhao, Shoubao Ma, Qiao Cheng, Yuan Song, Yonghao Liu, Ziling Zhu, Huirong Chang, Xiao Yu, Aining Sun, Yi Zhang, Dario A. A. Vignali, Depei Wu, Haiyan Liu (2015) IL-35 mitigates murine acute graft-versus-host disease with retention of graft-versus-leukemia effects. Leukemia 29: 939-46
10. Shoubao Ma, Qiao Cheng, Yifeng Cai, Huanle Gong, Yan Wu, Xiao Yu, Liyun Shi, Depei Wu, Chen Dong, and Haiyan Liu (2014) IL-17A produced by γδ T cells promotes tumor growth in hepatocellular carcinoma. Cancer Research 74(7): 1969-82

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