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靶向非经典人类白细胞抗原作为癌症新型治疗策略

英文原题:Targeting of Non-Classical Human Leukocyte Antigens as Novel Therapeutic Strategies in Cancer.

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Targeting of Non-Classical Human Leukocyte Antigens as Novel Therapeutic Strategies in Cancer.

PubMed 2024/12/22(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

人类白细胞抗原(HLA)是对抗癌症免疫应答的重要调节因子,其中经典 HLA 在肿瘤识别和免疫监视中的作用已被充分记录。近年来,非经典 HLA——包括 HLA-E、HLA-F、HLA-G 和 HLA-H——因其在免疫调节中多样且较为非常规的功能,已成为癌症免疫景观中的关键参与者。这些分子展现出独特机制,使肿瘤能够逃避免疫检测、促进肿瘤进展,并导致治疗耐药。本综述全面审视了目前对实体癌中非经典 HLA 的理解,重点关注它们在塑造肿瘤微环境和影响免疫应答中的具体作用。通过分析 HLA-E、HLA-F、HLA-G 和 HLA-H 如何调节与免疫细胞(如 T 细胞、NK 细胞和抗原呈递细胞)的相互作用,我们强调了这些分子促成免疫逃逸和转移的关键通路。

此外,我们综述了针对非经典 HLA 的有前景的治疗策略,包括可能通过逆转肿瘤内免疫抑制来提高癌症治疗结果的新兴免疫疗法。理解这些非经典 HLA 在实体癌中的影响,可能为癌症免疫学提供新的见解,并可能促成创新且更有效的免疫治疗方法的开发。本综述强调了非经典 HLA 作为潜在治疗靶点的重要性,为癌症免疫治疗不断发展的领域中的未来研究提供了必要基础。

展开英文摘要原文

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.

论文信息

作者
Benitez Fuentes JD、Bartolome Arcilla J、Mohamed Mohamed K、Lopez de Sa A、de Luna Aguilar A、Guevara-Hoyer K、Ballestin Martinez P、Lazaro Sanchez AD
第一作者单位
Department of Medical Oncology, Elche General University Hospital, 03203 Elche, Spain.Spain
通讯作者单位
Department of Immunology, IML and IdISSC, Hospital Clinico San Carlos, 28040 Madrid, Spain.Spain
文献类型
综述
期刊
Cancers2024 Dec 22
原文标识
PubMed 39766165 · DOI 10.3390/cancers16244266