Abstract
Relevance: Hepatocellular carcinoma (HCC) is one of the most aggressive and deadly malignant tumors, characterized by treatment complexity and high resistance to immunotherapy. Alpha-fetoprotein (AFP) is traditionally used as a diagnostic marker for HCC. Recent studies reveal its key role in carcinogenesis and in forming a tolerogenic microenvironment that suppresses the anti-tumor immune response. Despite numerous publications, contradictions remain in assessing AFP’s functions and prognostic value, necessitating an analytical review. This study aimed to summarize current data on AFP’s role in tumor immune evasion mechanisms and to evaluate its potential as a target for novel immunotherapeutic approaches for HCC treatment. Methods: A systematic search and analysis of publications on AFP and HCC were conducted in PubMed and Google Scholar, and several specialized medical and scientific journals (including Cancer Research) from 2017 to 2025. Keywords included: “alpha-fetoprotein”, “hepatocellular carcinoma”, “immunosuppression”, “tumor immune evasion”, “AFP immunomodulation”, “immune response in HCC”. Selected articles met relevance and novelty criteria. Results: The review revealed that AFP plays a central role in HCC progression through its immunosuppressive effects and activation of tumor immune evasion mechanisms. Contradictions in prognostic data reflect the complexity and multilayered biological functions of AFP. Conclusion: AFP is not only a key diagnostic marker for HCC but also plays an active role in establishing immune tolerance. Its ability to suppress antitumor immune response makes AFP a promising therapeutic target, especially in combined immunotherapeutic approaches aiming to improve treatment efficacy.