Congratulations our Postdoctoral Researcher Liang Zhixian for new paper in Cancer cells
Our lab has achieved a monumental milestone in oncology research. Led by Professor Alfred Cheng Sze-lok, the research team has successfully uncovered a novel mechanism driving resistance to immunotherapy in liver cancer. This groundbreaking study has been officially published in the prestigious international scientific journal Cancer Cell and has garnered extensive coverage from major local and online media outlets.
A high-profile press conference hosted by the faculty attracted 9 leading media organizations. Comprehensive coverage was broadcasted and published across major electronic, print, and online news platforms—including TVB News, Cable News, Sing Tao Daily News, HKET, Oriental Daily, am730, Epoch Times, and Medical Inspire. The media heavily spotlighted how this research addresses a critical bottleneck in advanced cancer treatment.
Liver cancer stands as the third leading cause of cancer-related deaths in Hong Kong. While immune checkpoint blockade (ICB) therapies, such as anti-PD-1 therapy, serve as the frontline treatment for advanced cases, over 80% of patients ultimately develop resistance, causing the treatment to fail.
Building upon the lab’s foundational discoveries regarding tumor adaptation, our team’s latest research details how a unique subtype of macrophages, known as TREM2+ LAM (Lipid-Associated Macrophages), contributes directly to this resistance. Normally acting as “scavengers” to eliminate dead or dying cells, these macrophages undergo a functional shift within the nutrient-depleted tumor microenvironment. Our lab discovered that TREM2+ LAM macrophages execute a dual “clear out-feed in” function. While clearing away apoptotic cells, they actively recycle fatty acids and transfer these lipids directly to cancer cells via extracellular vesicles. This metabolic supply line not only nourishes the tumor but also reprograms the gene expression of cancer cells, making them highly resistant to immune system attacks.
To break this resistance loop, the research team developed a novel combination strategy pairing standard PD-1 inhibitors with a targeted TREM2 inhibitor. In preclinical mouse models that were previously non-responsive to conventional immunotherapy, this combination approach yielded exceptional results. After a four-week regimen, the tumors shrank significantly without causing notable side effects, such as behavioral changes or weight loss.
Furthermore, the team established that the levels of TREM2+ LAM can be tracked via a simple blood test, offering a non-invasive tool to predict patient resistance and deliver truly personalized, precision care.
“We have successfully applied for a patent on utilizing TREM2+ LAM targeting strategies to enhance immunotherapy efficacy,” stated Professor Alfred Cheng. Our lab is currently collaborating with pharmaceutical partners to prepare for upcoming clinical trials, with efficacy and safety findings anticipated within the next two to three years.
Clinical statistics suggest that this combination therapy could potentially benefit 40% to 50% of advanced liver cancer patients who currently experience immunotherapy failure, potentially extending their survival by 20% to 30%. Strikingly, data analysis reveals that this TREM2+ LAM-driven resistance pattern is also highly active in other aggressive malignancies, such as triple-negative breast cancer and non-small cell lung cancer. This indicates that the laboratory’s findings could possess far-reaching therapeutic implications across multiple cancer types.
Our Lab remains committed to translating these mechanistic biological insights into effective clinical interventions, bringing new hope to cancer patients worldwide.
Stay tuned for more updates from our lab and our continuous efforts in cancer research.