The role of γδ T cells, innate-like lymphocytes with unrestrained MHC, in various malignancies has recently been extensively studied. However, there is limited research regarding γδ T cells in ovarian cancer (OC) patients. Here, we investigated the distribution patterns of γδ T cells and their main subsets in peripheral blood and tumor tissues among OC patients, benign ovarian tumor (BOT) patients, and age-matched healthy controls (HC) by flow cytometry, as well as the expression levels of IFN-γ and IL-17A secreted from γδ T cells. Immunohistochemical staining was utilized to detect the numbers of γδ T cells and their main subsets in different types of ovarian tumor tissues. Additionally, we also investigated chemotaxis effects on γδ T cells, as well as their cytotoxic activity and proliferation. We found that the percentages of γδ T cells and Vδ1 T cells were significantly higher in OC tissues than BOT tissues and normal (N) ovarian tissues, while there were no obvious differences in peripheral blood. Meanwhile, higher numbers of γδ T cells and Vδ1 T cells were observed in OC tissues, and were positively related to advanced clinicopathological features of OC patients. Further, the levels of IFN-γ secreted by γδ T cells were relatively lower, while IL-17A was expressed at a high level in both the peripheral blood and tissues of OC patients. Chemotaxis assay revealed that supernatants derived from OC tissues possessed a stronger capacity to attract and recruit γδ T cells. However, γδ T cells sorted from OC tissues showed weakened cytotoxic activity against ovarian cancer cells, and γδ T cells cocultured with OC tissue supernatants could effectively inhibit the proliferative activity of naïve CD4+ T cells. These data suggested that γδ T cells might have critical roles in OC progression and potential utilization in treatment approaches or prognosis prediction.

Perineurial network (PNN) is a special extracellular matrix structure in the central nervous system, and its alterations are associated with the pain hypersensitivity. Recent studies have suggested a potential interaction between abnormal activation of spinal microglia and PNN. This study investigates whether S-ketamine mitigates neuropathic pain via inhibiting degradation of PNNs by spinal microglia. C57BL/6 mice were utilized for CCI modeling to induce neuropathic pain. Subsequent to modeling, we assessed the expression changes of spinal microglia, PNN and inflammatory factors. Microglia colocalization with PNN was evaluated via 3D reconstruction to quantify spatial overlap. Minocycline was administered to target microglia. S-ketamine was subsequently administered to CCI mice, and its effects on pain behavior, microglial activation, and PNN were investigated. Microglia–PNN colocalization was evaluated via 3D reconstruction to quantify spatial overlap. CCI mice exhibited significant neuropathic pain, accompanied by increased microglia-mediated phagocytosis of PNN. Minocycline and S-ketamine treatment of CCI mice led to improved pain thresholds, suppression of neuroinflammation, and reduction in microglia-mediated phagocytosis of PNN. Increased microglial phagocytosis leading to PNNs degradation in the spinal dorsal horn plays a critical role in neuropathic pain pathogenesis. The analgesic effects of S-ketamine may be attributed to its modulation of this mechanism.