Prakash Kruthika, Rajendran Ramya Lakshmi, Dhayalan Sanjana, Gangadaran Prakash, Ahn Byeong-Cheol, Aruljothi Kandasamy Nagarajan
Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603203, India.
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Cells. 2025 Jul 16;14(14):1087. doi: 10.3390/cells14141087.
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.
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，从惰性的乳头状甲状腺癌（PTC）到快速进展且致命的间变性甲状腺癌（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，但治疗耐药性和预后不良仍是晚期和未分化型甲状腺癌的主要挑战。目前，人们越来越关注自然杀伤（NK）细胞作为一种有前景的免疫治疗途径的潜力。这些先天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）的影响，该微环境会抑制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。我们还讨论了基于NK细胞的免疫疗法的最新进展，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使用的策略。此外，还介绍了新兴的模式，如NK细胞衍生的细胞外囊泡。通过将机制性见解与先进的治疗技术相结合，本综述全面阐述了基于NK细胞的干预措施及其在改善甲状腺癌患者预后方面的未来潜力。
