Our research centers on deciphering how nutrients affect immune responses of an array of immune cells through the unexplored metabolic regulations and to investigate how metabolic reprogramming and targeting can be harnessed to fine-tune immune responses in diseases, especially tumor immunity and autoimmune.
Metabolic adaptation of T cells
Metabolic stress imposed by the tumor microenvironment and peripheral tissues to CD8 T cells and other tissue-resident T cells challenges cellular behaviors. In this research theme, we would like to decipher how these regulations tailor T cell behavior and differentiation program by intervening signaling, epitranscripome, and proteome.
Metabolic crosstalk during immuosurveillance
Metabolic competition and communication between cancer cells and their neighboring immune cells determines the amplitude and type of immune response. In this direction, we would like to understand how this communication influence immune cell’s behavior and metabolic makeup of cancer cells uring tumorigenesis.
Firing up immune ignorant tumor
Lack of T cell infiltration in tumors represents one of the major barriers of effective cancer immunotherapy, especially checkpoint blockade. In this project, we would like to understand how we can fire up cold tumors to synergize with current immunotherapy and aim to define new types of immunotherapies for cancer treatment.
Immunometabolic regulations in macrophages
The functional plasticity of macrophages is tightly regulated by cytokines. In vivo, metabolic activities of macrophages have been revealed to play a new layer of regulation to orchestrate macrophage activities. We would like to decipher how these metabolic regulations, especially mitochondrial processes, guide macrophage activation and shape their functions in tumor and inflammatory diseases.
Exosome and immunometabolic regulations
Exosome released by dendritic cells play a critical role on guiding T cell activation. However, it remains unclear if it regulates T cell metabolism. Here, we would like to explore this and aim to exploit novel approaches for vaccine design and cancer immunotherapy.
- Wan-Chen Cheng, Yao-Chen Tsui, Simone Ragusa, Marco Mina, Viktor Koelzer, Fabien Franco, Heinz Laubli, Benjamin Tschumi, Alfred Zippellius, Daniel Speiser, Pedro Romero, Tatian Petrova, Kirsten Mertz, Giovanni Ciriello, Ping-Chih Ho (2019) Uncoupling protein 2 reprograms the tumor microenvironment supporting anti-tumor immune cycle. Nat. Immunol. 20; 206-217.
Pu-Ste Liu, Haiping Wang, Xiaoyun Li, Tung Chao, Stefan Christen, Giusy Di Conza, Wan-Chen Cheng, Chih-Hung Chou, Magdalena Vavakova, Charlotte Muret, Koen Debackere, Massimiliano Mazzone, Hsien-Da Hung, Sarah Maria-Fendt, Julijana Ivanisevic, Ping-Chih Ho (2017) a-Ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat. Immunol. 18; 985-994.
Daniel Thommen, Viktor Koelzer, Petra Herzig, Andreas Roller, Marcel Trefny, Sarah Dimeloe, Anna Kiialainen, Jonathan Hanhart, Catherine Schill, Christoph Hess, Spasenija Savic Prince, Mark Wiese, Didier Lardinois, Ping-Chih Ho, Christian Klein, Vaios Karanikas, Kirsten Mertz, Ton Schumacher, Alfred Zippelius (2018) A transcriptionally and funcationally distinct CD8+ T cell pool with predictive potential in non-small cell lung cancer. Nat. Med. 24; 994-1004.
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