Human leukocyte antigens (HLAs) are essential regulators of immune responses against cancer, with classical HLAs well-documented for their role in tumor recognition and immune surveillance. In recent years, non-classical HLAs—including HLA-E, HLA-F, HLA-G, and HLA-H—have emerged as critical players in the immune landscape of cancer due to their diverse and less conventional functions in immune modulation. These molecules exhibit unique mechanisms that enable tumors to escape immune detection, promote tumor progression, and contribute to therapeutic resistance. This review provides a comprehensive examination of the current understanding of non-classical HLAs in solid cancers, focusing on their specific roles in shaping the tumor microenvironment and influencing immune responses. By analyzing how HLA-E, HLA-F, HLA-G, and HLA-H modulate interactions with immune cells, such as T cells, natural killer cells, and antigen-presenting cells, we highlight key pathways through which these molecules contribute to immune evasion and metastasis. Additionally, we review promising therapeutic strategies aimed at targeting non-classical HLAs, including emerging immunotherapies that could potentially enhance cancer treatment outcomes by reversing immune suppression within tumors. Understanding the influence of these non-classical HLAs in solid cancers may offer new insights into cancer immunology and may lead to the development of innovative and more effective immunotherapeutic approaches. This review underscores the importance of non-classical HLAs as potential therapeutic targets, providing a necessary foundation for future studies in the evolving field of cancer immunotherapy.
人类白细胞抗原（HLAs）是调控抗肿瘤免疫应答的关键分子，其中经典HLA在肿瘤识别与免疫监视中的作用已得到充分证实。近年来，非经典HLA（包括HLA-E、HLA-F、HLA-G和HLA-H）因其在免疫调节中独特且非传统的作用机制，已成为癌症免疫微环境中的重要参与者。这些分子通过特殊机制帮助肿瘤逃避免疫识别、促进肿瘤进展并导致治疗抵抗。本综述系统梳理了当前对实体瘤中非经典HLA的认知，重点探讨其在塑造肿瘤微环境和调控免疫应答中的具体作用。通过分析HLA-E、HLA-F、HLA-G和HLA-H如何调节与T细胞、自然杀伤细胞及抗原呈递细胞等免疫细胞的相互作用，我们揭示了这些分子介导免疫逃逸和转移的关键通路。此外，本文综述了针对非经典HLA的治疗策略，包括通过逆转肿瘤内免疫抑制来提升疗效的新型免疫疗法。深入理解非经典HLA在实体瘤中的作用机制，可为癌症免疫学研究提供新视角，并推动创新高效免疫疗法的开发。本综述强调了非经典HLA作为潜在治疗靶点的重要性，为癌症免疫治疗领域的发展奠定了必要的研究基础。
Targeting of Non-Classical Human Leukocyte Antigens as Novel Therapeutic Strategies in Cancer
肿瘤(癌症)患者之家