研究概要
甲状腺癌是最常见的内分泌肿瘤,由一组异质性的组织学亚型组成,从惰性的甲状腺乳头状癌(PTC)到快速进展且致命的甲状腺未分化癌(ATC)。
中文摘要
甲状腺癌是最常见的内分泌肿瘤,由一组异质性的组织学亚型组成,涵盖从惰性的甲状腺乳头状癌(PTC)到快速进展且致命的甲状腺未分化癌(ATC)。尽管传统疗法,如手术和放射性碘(RAI),对分化型甲状腺癌有效,但治疗耐药和不良预后仍然是晚期和未分化型甲状腺癌的主要挑战。当前,越来越多的关注指向自然杀伤(NK)细胞作为有前景的免疫治疗途径的潜力。这些固有免疫细胞能够直接对肿瘤细胞产生细胞毒性,但其效率常常受到免疫抑制性肿瘤微环境(TME)的损害,后者抑制NK细胞的激活、浸润和持久性。本综述探讨了甲状腺癌中NK细胞与TME之间的动态相互作用,详细阐述了免疫逃逸的关键机制,包括抑制性细胞因子的影响、趋化因子格局的改变以及抑制性配体的表达。我们进一步讨论了基于NK细胞的免疫治疗的最新进展,包括体外扩增、基因修饰以及与检查点抑制剂或细胞因子联合治疗的策略。此外,还讨论了新兴模式,如NK细胞来源的细胞外囊泡。通过将机制性见解与不断进步的治疗技术相结合,本综述提供了关于基于NK细胞的干预措施及其在改善甲状腺癌患者预后方面未来潜力的全面视角。
展开英文摘要原文
Thyroid cancer, the most frequently occurring endocrine neoplasm, comprises a heterogeneous group of histological subtypes, spanning from the indolent papillary thyroid carcinoma (PTC) to the rapidly progressive and lethal anaplastic thyroid carcinoma (ATC). Although conventional therapies, such as surgery and radioactive iodine (RAI), are effective for differentiated thyroid cancers, treatment resistance and poor prognosis remain major challenges in advanced and undifferentiated forms. In current times, growing attention has been directed toward the potential of Natural Killer (NK) cells as a promising immunotherapeutic avenue. These innate immune cells are capable of direct cytotoxicity against tumor cells, but their efficiency is frequently compromised by the immunosuppressive tumor microenvironment (TME), which inhibits NK cell activation, infiltration, and persistence. This review explores the dynamic interaction between NK cells and the TME in thyroid cancer, detailing key mechanisms of immune evasion, including the impact of suppressive cytokines, altered chemokine landscapes, and inhibitory ligand expression. We further discuss latest advancements in NK cell-based immunotherapies, including strategies for ex vivo expansion, genetic modification, and combinatorial approaches with checkpoint inhibitors or cytokines. Additionally, emerging modalities, such as NK cell-derived extracellular vesicles, are addressed. By combining mechanistic insights with advancing therapeutic techniques, this review provides a comprehensive perspective on NK cell-based interventions and their future potential in improving outcomes for patients with thyroid cancer.
论文信息
- 作者
- Prakash K、Rajendran RL、Dhayalan S、Gangadaran P、Ahn BC、Aruljothi KN
- 单位
- Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603203, India.India
- 文献类型
- 综述
- 期刊
- Cells2025 Jul 16