Metabolic crosstalk during immuosurveillance in tumorigenesis

Metabolic competition and communication between tumor cells and their neighboring immune cells determines the amplitude and type of immune responses. In this direction, we would like to understand how this communication influence immune cell’s behavior and metabolic makeup and immunogenicity of tumor cells during tumorigenesis. In addition, we are exploring how metabolic modulation provided by immune cells can drive cancer metastasis and epigenetic reprogramming for cancer evolution.

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Firing up immune ignorant tumor

Lack of T cell infiltration in tumors represents one of the major barriers of effective cancer immunotherapy, especially immune checkpoint blockade treatment. 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. Moreover, we aim to elucidate how the spatial and functional interactions among cells within the tumor microenvironment could support the quantity and quality of CD8+ TILs.

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Metabolic adaptation in T cells in the context of tumors and chronic viral infection

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 with particular focuses on T cell exhaustion and differentiation and tissue context-dependent behaviours in regulatory T cells.
 

Immunometabolic regulations in innate immune cells

The functional plasticity of macrophages and dendritic cells is tightly regulated by cytokines and pattern recognition receptor singling. Intriguingly, metabolic programs in these innate immune cells have been revealed to play a new layer of regulation to orchestrate their functionality both in vitro and in vivo. We would like to decipher how these metabolic regulations, especially mitochondrial processes, guide activation and orchestrate functional polarization in these innate immune cells in tumors and inflammatory diseases.

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Tumor and peripheral crosstalk

We are exploring the cellular migration pattern and functional changes during tumor progression. Moreover, we are developing strategies based on this migratory regulation for remodelling immune responses against solid tumor and designing next generation CAR T-cell therapy.

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Hepatocellular carcinomas and NASH

By harnessing the specialised immune surveillance engaged in liver, we are testing how myeloid cells in liver instruct T cell immune responses in the contexts of liver damages, hepatocellular carcinoma, and NASH. Moreover, we developed antibody-based treatment to reprogramming the tumor microenvironment in hepatocellular carcinomas. Our goal is to develop innovative strategies for treating hepatocellular carcinomas and unveiling the biology in liver cancer. To achieve that, we also develop human HCC ex vivo platform for immunoprofiling and screening of therapeutic modality.

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