Characterizing Inflammatory Links in Liver Cancer
The past few years yielded an explosion of exciting clinical trials showing the remarkable benefit of immune treatments in cancer patients. The link between inflammation and cancer is now established, yet the underlying molecular mechanisms are unresolved. As tumors progress, they modulate the inflammatory cells towards a protumorigenic immunosuppressive phenotype. We have shown that the inflammatory cells reciprocate by sculpting the parenchymal epithelial cells. We are studying these reciprocal interactions and hypothesize that they lie at the heart of the link between inflammation and cancer.
Liver cancer is the third most common cause of cancer-related death worldwide, and its dramatic three decades-long rise makes liver cancer the fastest-growing cause of deaths from cancer in the United States. Liver cancer is a prototype of inflammation induced cancer. We employ several strategies to analyze the changes that occur in inflammatory cells before and after liver tumor emergence, based on our preliminary findings showing that changes in inflammatory cells precede tumorigenesis. We are comprehensively mapping the changing inflammatory microenvironment in mouse models of inflammation induced Hepatocellular carcinoma (HCC) – the most common form of primary liver cancer. Using genetic manipulation strategies, coupled with cell isolation techniques we are delineating the molecular cues that mediate these changes and are analyzing the functional role of key mediators of these processes in the malignant process.
We have recently characterized a new form of inflammation which is characterized by the presence of focal collections of immune cells (also known as ectopic lymphoid like structures). Surprisingly, this form of inflammation promotes cancer growth by hijacking molecules which are secreted by lymphocytes, which are usually associated with anti-tumor responses. We are now testing how the new and exciting immune check point drugs interact with these foci. This could impact immunotherapy of cancer, wherein lymphocytes are usually considered positive mediators of anti-cancer responses.