Pro and Anti tumorigenic functions of tertiary lymphoid structures

The different roles of the adaptive immune system in cancer are beginning to unfold. The dramatic responses to immune check point drugs in some tumors generated an accelerated need for understanding the complex set of interactions between tumor and immune cells. In view of the major pathophysiological role of immune cells in hepatocellular carcinoma it is not surprising that malignant hepatocytes interact extensively with adaptive immune cells, resulting in both pro-tumor immunopathology and anti-tumor protective immunity. Identifying potential responders to drugs that target the adaptive immune system, monitoring their immune response to the tumor and devising the best treatment combinations depends on understanding the complex set of interactions taking place within the tumor and in the adjacent hepatic parenchyma. Cellular infiltration usually entails a diffuse influx of immune cells, scattered throughout the inflamed tissue. However, infiltrating leukocytes often form ectopic lymphoid aggregates or even more complex structures that histologically resemble lymphoid organs. These structures direct various B and T cell responses and are referred to as ectopic lymphoid-like structures (ELSs). ELSs often develop at sites of chronic inflammation where they can influence the course disease. In many cancers, the presence of ELSs correlates with a better prognosis and they may coordinate endogenous antitumor immune responses. Surprisingly, in the liver – ELSs have diverse roles – while intratumoral ELS are associated with a good prognosis, the presence of ELSs in the liver parenchyma is positively correlated with HCC. We are currently dissecting the potential role of immunosuppression in ELS protumorigenic function and aiming to identify ways to restore functional immunity upon ELSs.