Reporter Qiu Junji / Taipei Report
Cancer immunotherapy has become an important weapon against cancer in recent years, but it is not effective for some patients. National Taiwan University Hospital analyzed pleural effusion from lung cancer patients that was originally to be discarded, and further research revealed that a "BET inhibitor," originally mainly used for a few cancers such as blood cancer and lymphoma, can act as an "energy drink" to restore vitality to exhausted immune cells, reawakening immunity. This may potentially enhance the effectiveness of immunotherapy in the future, bringing hope to more patients.
National Taiwan University Hospital held a research results press conference today. Dr. Cai Xinzhen, Deputy Director of the Advanced Medical Center and a thoracic physician, stated that lung cancer is the leading cause of cancer death in Taiwan and globally, with over 40% of cases diagnosed at an advanced stage. Current treatments for advanced lung cancer include chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Among these, immune checkpoint inhibitors primarily release the "brakes" on immune T cells, allowing the immune system to more aggressively attack cancer cells, but some patients have limited efficacy, partly due to severe T cell exhaustion.
Dr. Cai pointed out that if cancer cells persist long-term, T cells are continuously stimulated and may become fatigued, forming "exhausted T cells." If they further enter a "terminal exhaustion" state, their function is almost locked, and existing immunotherapy is difficult to reverse.
To overcome this bottleneck, the NTU research team targeted malignant pleural effusion from advanced lung cancer patients. Dr. Cai explained that when patients experience breathing difficulties due to pleural effusion, the fluid is typically drained. These samples, originally to be discarded, actually contain cancer cells, T cells, and various immune cells in a highly immunosuppressive environment, making them an important source for studying exhausted T cells.
Using T cells from patient pleural effusion, the research team conducted systematic drug screening and found that epigenetic drugs and "BET inhibitors" have the potential to reactivate terminally exhausted T cells. Dr. Cai explained that epigenetic drugs differ from conventional therapies such as chemotherapy. Chemotherapy mainly works by killing cancer cells directly, while these drugs change the internal gene expression of immune cells, adjusting cell state rather than directly killing cancer cells.
Dr. Cai noted that BET inhibitors are not new drugs; they were originally developed to directly attack cancer cells, and some have entered clinical trials. However, due to high doses, side effects and cytotoxicity were significant, preventing widespread use. This study found that if the goal is to activate T cells, the required dose can be lower, potentially balancing efficacy and safety.
Further research revealed that BET inhibitors alter T cell metabolic states, thereby restoring immune function and reducing the proportion of terminally exhausted T cells. In mouse models of lung cancer and melanoma, BET inhibitors also showed tumor growth suppression. The research results were published in the international authoritative medical journal Nature Immunology in May of this year.
Regarding the effect of BET inhibitors demonstrated in this study, NTU Hospital Superintendent Yu Zhongren described it as akin to a student about to give up on an exam suddenly regaining spirit and combat effectiveness after drinking an energy drink. Dr. Cai said that in the future, BET inhibitors could be combined with current immunotherapy and cell therapies such as CAR-T to further enhance anticancer effects, hoping to benefit more patients who do not respond well to immunotherapy.
