Cellular and Molecular Oncoimmunology Lab

The challenge

Hepatocellular carcinoma (HCC), the prevailing form of primary liver neoplasms, is prototypically an inflammation-driven cancer developing after years of chronic insults and with still unsatisfactory therapeutic options. Using HCC as a paradigm of cancer inflammation, we are seeking to answer two central questions: What are the pathways subverting anti-tumor immunity and the major players driving immune evasion? In which way can the immune system be manipulated to evoke or enhance spontaneous and therapy-induced tumor control?

To answer them, we will take advantage of cutting-edge approaches such as unique genetically engineered mouse models, patient-derived tissue platforms, next-generation sequencing, bioinformatics, molecular biology, live imaging, flow, and mass cytometry.

Main research areas

Establishing the role of conventional dendritic cells (cDCs) in liver carcinogenesis

cDCs represent the prototype of antigen-presenting cells, they sense microenvironmental signals and recognize pathogens. Activation of cDCs leads to different effector functions ranging from the activation of cytotoxic lymphocytes to tolerance. Among cDCs, type 1 conventional DCs (cDC1) have emerged as key players in the cross-priming of tumor-specific lymphocytes and in the response to cancer immunotherapy.  After conducting a deep cellular and molecular profiling of the immune compartment in different syngeneic tumor models, including liver cancer, we observed the presence of transcriptionally distinct cDC states. Based on these observations we hypothesized that, within tumor tissues, cDCs can acquire unique phenotypes to either buildup or regulate anti-tumor immune responses.

Analysis of systemic inflammatory responses in liver cancer and human validation

Cancer is a complex multifactorial disease that continuously evolves during progression and treatment. To understand the interplay between local inflammatory response and systemic immune changes, we will study, at the single-cell level, the transcriptional changes occurring within the leukocyte compartment during liver cancer progression and treatment. Finally, an innovative patient-derived tumor explant platform, that recapitulates the complexity of human tumor architecture, will be implemented to test the implications of our preclinical work in human settings.