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Invited talk 3
Prof. Alfred Sze Lok CHENG

School of Biomedical Sciences,
The Chinese University of Hong Kong

Dr. Cheng is a Professor in the School of Biomedical Sciences and an Assistant Dean (Research) of the Faculty of Medicine at the Chinese University of Hong Kong (CUHK). He obtained his Ph.D. on hepatitis B and liver cancer under the mentorship of Prof. Joseph Sung at CUHK in 2002 and postdoctoral training on cancer epigenetics from Prof. Tim Huang’s lab at the Ohio State University. His current work focuses on the epigenetic and transcriptional regulation in tumor-immune ecosystem, with strong links to computational and clinician scientists for translational research. The major objective is to unravel the cellular and molecular basis of therapeutic resistance to facilitate rational design of mechanism-based immunotherapy for cancer patients.

Topic:  Translating epigenetic mechanism discoveries into cancer immunotherapies

Summary: Immune-checkpoint blockade (ICB) therapies have transformed the treatment landscapes of solid malignancies including hepatocellular carcinoma (HCC), which is currently the sixth most common cancer and the third leading cause of cancer death worldwide. Despite unprecedented success in clinical trials, the strong immunosuppressive tumor microenvironment (TME) prohibits sufficient CD8+ tumor-infiltrating lymphocytes (TILs), thus restricting the responsiveness of anti-programmed cell death-(ligand) 1 (anti-PD-[L]1) to a minority of HCC patients. Understanding of cancer epigenomes provides new opportunities to rewire the transcriptional network that drives hallmark tumor traits. In addition to the capability to alter cancer cell-intrinsic phenotypes, epigenetic therapies might also antagonize the microenvironmental factors underpinning the resistance to ICB. Our recent proof-of-concept studies have demonstrated that epigenetic remodeling of TME can cause immunosuppressive myeloid cell inhibition and TIL recruitment, thus synergizing anti-tumor responses with anti-PD-(L)1 therapies in preclinical models. The discoveries of epigenetic mechanisms in tumor-immune ecosystem will reinforce immunotherapy and identify patients who will most likely undergo a good response to the treatment.

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