Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence

SIMPLE SUMMARY: Locoregional therapies such as surgical resection, liver transplantation, and ablative techniques are preferred for early-stage HCC management. However, 70–80% of patients report HCC recurrence within 5 years of curative treatment. During the initiation and establishment of carcinogenesis, malignant cells suppress the anti-tumor immune surveillance system of the host. Therefore, modification of the immune contexture plays a crucial role in prognosis and recurrence. Following curative treatment, enhancement of effector immune cells confers effective anti-tumor immunity and good prognosis, while suppression of effector immune cells and enrichment of immunosuppressant cells promotes poor prognosis and recurrence. A combination of immunotherapeutic approaches with curative or systemic treatment may enrich effector immune molecules, surpass the immunosuppressive signals, and improve the treatment response. ABSTRACT: Hepatocellular carcinoma (HCC) is often recognized as an inflammation-linked cancer, which possesses an immunosuppressive tumor microenvironment. Curative treatments such as surgical resection, liver transplantation, and percutaneous ablation are mainly applicable in the early stage and demonstrate significant improvement of survival rate in most patients. However, 70–80% of patients report HCC recurrence within 5 years of curative treatment, representing an important clinical issue. However, there is no effective recurrence marker after surgical and locoregional therapies, thus, tumor size, number, and histological features such as cancer cell differentiation are often considered as risk factors for HCC recurrence. Host immunity plays a critical role in regulating carcinogenesis, and the immune microenvironment characterized by its composition, functional status, and density undergoes significant alterations in each stage of cancer progression. Recent studies reported that analysis of immune contexture could yield valuable information regarding the treatment response, prognosis and recurrence. This review emphasizes the prognostic value of tumors associated with immune factors in HCC recurrence after curative treatment. In particular, we review the immune landscape and immunological factors contributing to early-stage HCC recurrence, and discuss the immunotherapeutic interventions to prevent tumor recurrence following curative treatments.