Adoptive NK and γδT Cell Immunotherapy in Neurodegenerative Disease: Modulating Neuroinflammation and Advancing Clinical Translation
Neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and post-stroke sequelae, and rare disorders, including amyotrophic lateral sclerosis and multiple system atrophy, are characterized by complex neuroinflammatory processes and pathogenic protein aggregation. Natural killer and γδT cells, as pivotal immune effector cells, possess unique immunoregulatory and pathologic protein clearance capabilities, making these cells promising candidates for adoptive immunotherapy strategies. This review comprehensively discusses the synergistic mechanisms by which natural killer and γδT cells cross the blood-brain barrier and eliminate pathogenic proteins. Moreover, the mechanisms by which these cells modulate neuroinflammation and eliminate autoreactive T cells in the central nervous system are elucidated. The multifaceted roles across various neurodegenerative conditions are explored and the potential for clinical translation is evaluated. This review aims to provide theoretical and practical guidance for the development of innovative immune cell-based therapies targeting neurodegenerative diseases by integrating current research advances and identifying existing challenges.