Non-Invasive Biomarkers for Immunotherapy in Patients with Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

SIMPLE SUMMARY: The search for non-invasive biomarkers is a hot topic in modern oncology, since a tissue biopsy has significant limitations in terms of cost and invasiveness. The treatment perspectives have been significantly improved after the approval of immunotherapy for patients with hepatocellular carcinoma; therefore, the quick identification of responders is crucial to define the best therapeutic strategy. In this review, the current knowledge on the available non-invasive biomarkers of the response to immunotherapy is described. ABSTRACT: The treatment perspectives of advanced hepatocellular carcinoma (HCC) have deeply changed after the introduction of immunotherapy. The results in responders show improved survival compared with Sorafenib, but only one-third of patients achieve a significant benefit from treatment. As the tumor microenvironment exerts a central role in shaping the response to immunotherapy, the future goal of HCC treatment should be to identify a proxy of the hepatic tissue condition that is easy to use in clinical practice. Therefore, the search for biomarkers that are accurate in predicting prognosis will be the hot topic in the therapeutic management of HCC in the near future. Understanding the mechanisms of resistance to immunotherapy may expand the patient population that will benefit from it, and help researchers to find new combination regimens to improve patients’ outcomes. In this review, we describe the current knowledge on the prognostic non-invasive biomarkers related to treatment with immune checkpoint inhibitors, focusing on serological markers and gut microbiota.