Abstract 1274: Hallmark of immune responses to multiple tumor-associated antigens (TAAs) in immunodiagnosis of hepatocellular carcinoma (HCC) and other solid tumors

Abstract

Abstract The immune system of the patient with cancer is a sensitive sensor of alterations in structure and/or function of participants in tumorigenesis pathways and is capable of making immune responses in the form of autoantibodies to tumor-associated antigens (TAAs). A hallmark of this immune response is the production of autoantibodies of multiple specificities indicating the activation of more than one tumorigenesis pathway. Novel autoantibodies appear prior to or coincident with clinical detection of transformation to cancer. Activation of more than one tumorigenesis pathway expressed as multiple autoantibodies to TAAs is a finding consistent with the synthetic lethality paradigm where mutation of more than one gene or in the case of cancer, more than one tumorigenesis pathway is required for malignant transformation. After analyzing 321 sera from patients with different type of cancer for autoantibodies to seven selected TAAs including p53, c-myc, cyclin B1, p62, KOC, IMP1 and Survivin, 34% of the sera had autoantibody to one TAA and 20% had two to six autoantibodies simultaneously. In a recent study, we have used a mini-array of 14 selected TAAs as an approach in the immunodiagnosis of HCC, and found that 68% of the sera contained one or more than one antibodies against these TAAs. In addition, this TAA array can identify 43.8% of HCC patients who had normal AFP levels in serum. Some autoantibodies appeared de-novo concurrent with conversion to malignancy. Many novel target antigens besides the above have been identified and shown to be participants in tumorigenesis. The immune system response to TAAs is a repository of information on partners in the synthetic lethality paradigm. Our study can also support the hypothesis that a customized TAA array used for detecting anti-TAA autoantibodies can constitute a promising and powerful tool for immunodiagnosis of HCC and other solid tumors. Citation Format: Liping Dai, Pei Li, Weihong Liu, Chenglin Luo, Eng M. Tan, Jianying Zhang. Hallmark of immune responses to multiple tumor-associated antigens (TAAs) in immunodiagnosis of hepatocellular carcinoma (HCC) and other solid tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1274. doi:10.1158/1538-7445.AM2015-1274