The various immunological roles of human alpha-fetoprotein (HAFP) and its correlation with hepatomas, i.e., hepatocellular carcinomas (HCCs), are not always addressed together in the biomedical literature even though HAFP has long been utilized as a biomarker for hepatomas. Although the well-being of the newborn, infant, and juvenile can be monitored by the measurement of age-dependent HAFP in biological fluid levels throughout these stages, the majority of clinical reports in these age groups

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... o not include hepatomas (except hepatoblastomas) because of their later onset. However, reports concerning the interaction of HAFP and immune-associated proteins and cells in HCC patients in both applied clinical research and investigational settings has gradually increased over the years; thus ,it has expanded our base knowledge of mounting an immunotherapeutic response against AFP in hepatomas. The different immune-associated proteins (cytokines, chemokines, interleukin, kinins) interacting with HAFP has remained less reported due to limitations of appropriate in vitro and in vivo models. Concomitantly, the advances in elucidating the various immunological activities of AFP are opening new vistas of knowledge regarding the physiological roles of AFP in the growth of HCC. The present review surveys HAFP as an immunologic response modifier and regulator for HCC and its use in the generation of AFP – sensitized lymphocytes. An attempt is also made to relate the AFP activities to HCC progression following immunotherapies. Hence, the present review was divided into two major sections; I) AFP structure and homologies in the immune response, and II) the therapeutic use of AFP in HCC patients in adult stages in both in vivo and in vitro models