Advances in γδ T cell-mediated immune surveillance in cervical cancer

Cervical cancer is one of the most common malignancies of the female reproductive system worldwide, and its development is closely associated with persistent infection with high-risk human papillomavirus (HPV). γδ T cells, as key effector cells bridging innate and adaptive immunity, exert unique and complex regulatory functions in tumor immune surveillance. However, the distribution patterns, functional polarization states, and antitumor mechanisms of distinct γδ T-cell subsets within the cervical cancer microenvironment have not yet been systematically elucidated, and the impact of HPV infection on the functional remodeling of γδ T-cell subsets remains controversial. This review summarizes the distribution characteristics and functional polarization states of the major γδ T-cell subsets, including Vδ1, Vδ2, and Vδ3 T cells, in the cervical cancer microenvironment. We further discuss the molecular mechanisms through which these subsets participate in immune surveillance via T-cell receptor (TCR) signaling, NKG2D-mediated recognition, Fas/FasL signaling, and cytokine secretion, and examine the regulatory effects of HPV infection on γδ T-cell subset remodeling. In addition, recent preclinical advances in γδ T-cell subset-based adoptive immunotherapy and combination strategies involving immune checkpoint blockade in cervical cancer are reviewed. Overall, this review aims to provide a theoretical basis and new perspectives for optimizing immunotherapeutic targets and developing individualized treatment strategies for cervical cancer.