Breakthrough for Cancer Immunotherapy! CMU President Mien-Chie Hung’s Research Team Published Their Research in Journal of Clinical Investigation
Date：July 18, 2019
China Medical University (CMU) President Mien-Chie Hung is a world famous cancer genetic scientist. President Hung’s research team cooperated with MD Anderson Cancer Center and found that the combined treatment of IL-6 antibodies and anti-T-cell immunoglobulin mucin-3 (anti-Tim-3) can overcome the drug resistance of cancer cell in immunological inhibition and enhance the efficacy of immunotherapy. This will greatly benefit cancer patients and is a significant breakthrough in Taiwan’s cancer immunotherapy.
The research finding “IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion” was published on the Journal of Clinical Investigation on July 18th, 2019. It received high attention and recognition from the international medical community and raised Taiwan’s reputation and competitiveness in the field of cancer treatment.
Immunotherapy has been regarded as a new hope for cancer treatment. The US Food and Drug Administration (FDA) has also approved a number of clinical therapeutic antibodies. However, there are still some hidden cancer cells that can survive from the attack of immune cells. “PD-L1 is an immunological checkpoint inhibitor, and its binding with PD-1 receptor of T cells can activates common suppressor signals. Besides, the function of cytotoxic T cells will be suppressed so that cancer cells can escape from the immune surveillance. Therefore, blocking PD-L1 or PD-1 has shown encouraging results in cancer treatments.” said President Mien-Chie Hung.
The research team also found that the glycosylation in cancer cells have the potential to become an effective biomarker in the therapy and help to enhance the patient’s treatment efficacy.
Glycosylation of immunoreceptors and ligands can modulate the activation of immune signaling and immune surveillance. PD-L1 is a highly glycosylated protein and its glycosylation can effectively enhance immunosuppression, which leads to the drug resistance of the immune checkpoint inhibition. However, it is unclear that how the carcinogenic signaling regulates PD-L1 glycosylation to induce immunosuppression. In this research, President Hung’s team discovered that Janus kinase activated by IL-6 interleukin will phosphorylate PD-L1, and then attracted N- Glycosyltransferases STT3A to catalyze PD-L1 glycosylation and maintain the stability of PD-L1.
In animal model, the combination of IL-6 antibodies and anti-Tim-3 can induce and enhance the tumor cytotoxicity of T cells. A positive correlation between the expression of IL-6 and PD-L1 was also observed in the liver tumor tissues.
This research done by President Hung’s research team not only identified the mechanisms underlying the regulation of PD-L1 glycosylation initiation in cancer cells, but also illustrated the combination of IL-6 antibodies and anti-Tim-3 to be an effective marker-guided therapeutic strategy. This is indeed an exciting result for patients who still suffer from poor cancer treatment outcomes.