February 23, 2023

Spatial and Functional Analysis of the Tumor Microenvironment in Hepato-cellular Carcinoma for Stratification and Personalized Therapy

5th Call, iDoc

Short Summary

This project focuses on understanding the close link of liver cancer to fatty liver diseases like NAFLD. We aim to map the progression of liver disease to cancer, study the molecular communication between liver cancer and surrounding components such as immune cells, and test potential cancer vulnerabilities.

Goals

Our main goals are:
1) Mapping Disease Progression: We aim to create a detailed map of how liver cells change and interact with their surrounding environment from the early stages of fatty liver disease to full-blown liver cancer.

2) Studying Cell Interactions: We plan to examine how liver cells and immune cells communicate at a molecular level during the progression of fatty liver disease. This involves identifying specific molecules that these cells use to interact with each other.

3)Testing for Cancer Vulnerabilities: Finally, we will experimentally test the most critical interactions we find between liver cells and immune cells to see if they play a direct role in the progression of fatty liver disease to liver cancer.

Significance

Liver cancer and fatty liver diseases are a major and growing health concern globally. This project is dedicated to enhancing our understanding of how these conditions interplay and to discovering new therapeutic approaches.

Background

Liver cancer, known medically as Hepatocellular Carcinoma (HCC), poses a major global health challenge and is intricately linked to metabolic disorders such as Nonalcoholic Fatty Liver Disease (NAFLD). NAFLD, a significant risk factor for liver cancer, is characterized by the accumulation of fat in liver cells, leading to potential cell death and ongoing inflammation. This can escalate to fibrosis (scarring), cirrhosis (extensive liver damage), and ultimately, liver cancer. NAFLD not only contributes to the development of liver cancer but also affects its progression, possibly by influencing the tumor’s microenvironment. This environment is composed of various cells, including immune cells, blood vessels, lymphatics, and cancer-associated fibroblasts, all of which engage in complex interactions with the cancer cells. The behavior and response of immune cells in this environment are critical to understanding how liver cancer progresses and how it responds to treatment. Recent advances in research, especially detailed studies examining individual cells and comprehensive tissue analyses, have begun shedding light on these complex interactions. However, determining the exact mechanisms through which metabolic changes in NAFLD influence the immune environment and contribute to the progression of liver cancer remains a significant challenge.