Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism

SIMPLE SUMMARY: Deregulated tumor metabolism is known to shape the tumor microenvironment and directly affect the local immune response, promoting tumor growth, metastasis, and resistance to treatment. However, the metabolic profile or tumor cells, and therefore, the composition of their microenvironment, are highly variable among patients and even within the same tumor, resulting in heterogeneous response rates to oncologic therapies, making patient selection a key issue. This review article focuses on non-invasive imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism. In addition to improved tumor detection, such imaging tools may be able to provide a more accurate characterization of the individual tumor and ultimately improve understanding, as well as guide personalized treatment regimens for patients with liver cancer. ABSTRACT: With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.