Detect and Expunge Concealed Tumors of the Liver

Overview

The investigators long-term goal is to identify molecular and immunological signatures that can be used as biomarkers to accurately predict early recurrence and inform immunotherapeutic strategies in patients with hepatocellular carcinoma (HCC) after hepatectomy. As an initial step toward this long-term investigation, represented by this proposal, the investigators aim to comprehensively and globally describe the patterns of autoantibody expressions, the possible role in disease outcomes, and the relationship between these autoantibodies to tumor-specific/tumor-associated antigens by histologic examination as well as to peripheral immune characteristics in HCC patients with or without recurrence after surgery.

The current methods for early detection and therapy for recurrent HCC are generally ineffective and mostly inaccessible to patients worldwide. Thus, there is an urgent unmet medical need to have a sensitive and accessible method for monitoring and guiding therapeutic strategy for HCC recurrence, which will improve the prognosis of patients. The investigators current understanding of the mechanisms underpinning the onset and progression of HCC recurrence is incomplete. While tumor-related factors, including tumor size, number and differentiation, and underlying liver disease, are known risk factors for recurrence following curative therapies; evidence suggests that the recurrent mechanism is also governed by complex, poorly understood host immune responses. Tumor- and liver-infiltrating immune cells on the progression and recurrence of HCC have been documented. Tumor-infiltrating lymphocytes are believed to inhibit tumor growth, improving the prognosis of human malignancies. Inflammatory cytokines, including members of the interleukin (IL) and IL-11, contribute to hepatocyte proliferation and are also associated with cancer development after surgery. Unlike primary HCC, relapsed tumors have a higher immune evasion characteristic due to the accumulation of inhibitory cytokines and molecules. Moreover, the tumor microenvironment also plays a key role in the recurrence of HCC. Many immunosuppressive mechanisms, such as increased regulatory T cells and myeloid-derived suppressor cells with decreased cytotoxic T cells, are implicated in HCC recurrence. Identifying panels of tumor antigens that elicit a humoral response may have utility in cancer screening, diagnosis, or prognosis. Such antigens may also have utility in designing immunotherapy against the disease. A proteomic-based approach for identifying tumor antigens that induce autoantibodies to tumor antigens can be detected using the Human Proteome (HuProt) arrays. The HuProt arrays, comprising 21,154 unique full-length proteins can be deployed to survey serum autoantibodies using primary or recurrent HCC samples. Likewise, profiling peripheral immune cell populations and cytokines will add another dimension to the landscape of HCC recurrence and host immune modulation. In summary, identifying novel molecular and immunological markers in circulation and/or cancerous tissues is desirable to predict the risk of early primary and recurrent HCCs. This, coupled with several promising forms of immunotherapy for HCC that are currently available can help guide future therapies for HCCs.