Health
Researchers identify unexpected drivers of cancer immunotherapy resistance
A research team from the LKS School of Medicine at the University of Hong Kong School of Medicine (HKUMed) has identified an unexpected factor in cancer immunotherapy resistance. It is the detrimental effect of chronic type I interferon signaling on the tumor-killing CD8.+ T cellsThese findings provided new insights into the development of depleted CD8+ T cells that no longer effectively limit tumor growth have highlighted new targets for improved immunotherapy. This research cell report.
Background
Immunotherapy, in which drugs reactivate the body’s immune system to fight disease, is becoming an increasingly popular first-line treatment for many types of cancer. Although many cancer patients benefit from it, the majority are still unresponsive to treatment or are rapidly developing treatment resistance. is the result of unknown factors.
Cancer is normally suppressed by the anti-tumor effector function of CD8.+ T cells. When these cancer-fighting T cells are exhausted (depleted CD8+ When the T cell (Tex), protective response is weakened, the tumor undergoes immune escape and grows uncontrollably. Prevention and reversal of Tex are major goals of cancer immunotherapy.However, with the eventual development of Tex that is resistant to immunotherapy, its Effectiveness Limited to 20-30%. This study aims to understand the drivers of terminal Tex and uncover new therapeutic targets to improve cancer immunotherapy.
research result
Research team reveals surprising adverse effects of chronic type I interferon (IFN-I)[1] Exposure to Tex development and immunotherapy resistance. Cancer patients resistant to immunotherapy also tended to show higher levels of her IFN-I signaling.
Through reanalysis of public patient datasets, immune cell cultures, and animal models, researchers showed that chronic IFN-I signaling promotes CD8+ Involvement of T-cell fate in terminal exhaustion through promotion of lipid peroxidation (LPO), accumulation of therapeutic resistance.
Research significance
Dr. Heidi Ling Guang Sheng, Assistant Professor of Biomedical Sciences at HKUMed, and her team used the noxious IFN-I-LPO pathway to act as a biomarker to advise patient treatment plans and to individualize patient therapy. We have identified that we can improve Additionally, further research into the role of IFN-I will pave the way for new therapeutic options to improve patient response to immunotherapy.
“These findings pave the way for new approaches to improve the efficacy of immunotherapy against cancer. , and safety,” said Dr. Ling.
About the research team
The research was led by Heidi Ling Guang Sheng, Ph.D., Assistant Professor, Department of Biomedical Sciences, HKUMed. PhD student Chen Weixin was the first author, assisted by her PhD student Teo Jia Ming Nickolas. Yau Siu-wah, research assistant. Dr. Melody Wong Yee-man, technical her manager of Hong Kong Science and Technology Parks Corporation. Other collaborators include Dr. Lok Chun-nam, Prof. Che Chi-ming, HKU’s National Key Synthetic Chemistry Research Institute and Department of Chemistry. Dr Javed Asif, Dr Huang Yuanhua, Professor Stephanie Ma Kwai-yee (Faculty of Biomedical Sciences, HKUMed).
sauce:
Journal reference:
Chen W. and others. (2022) Chronic type I interferon signaling promotes depletion of terminal CD8+ T cells by lipid peroxidation and suppresses anti-PD-1 effects. cell report. doi.org/10.1016/j.celrep.2022.111647.
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