Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients

Abstract

Glioblastoma is the most common primary malignant brain tumor, and median survival is relatively short despite aggressive standard treatment. Natural killer (NK) cell dysfunction is strongly associated with tumor recurrence and metastasis but is unclear in glioblastoma. NK activity (NKA) represents NK cell-secreted interferon-γ (IFN-γ), which modulates immunity and inhibits cancer progression. This study aimed to analyze NKA in glioblastoma patients to obtain a clearer overview of immunity surveillance. From 2020 to 2021, a total of 20 patients and six healthy controls were recruited. Peripheral blood samples were collected preoperatively and on postoperative days (POD) 3 and 30. Then, NKA was measured using the NK VUE kit. Although NKA decreased on POD3, it recovered and further significantly enhanced on POD30, with a nearly five-fold increase compared to baseline (p = 0.004). Furthermore, the percentage of CD56brightCD16− NK cells decreased significantly on POD3 (p = 0.022) and further recovered on PO30. Subgroup analysis of extent surgical resection further revealed that the recovery of impaired NKA was attributable to gross total resection (GTR) rather than subtotal resection (STR). In conclusion, NKA is significantly impaired in glioblastoma, and GTR has demonstrated superior benefit in improving the suppressed NKA and increased CD56brightCD16− NK subset in glioblastoma patients, which may be associated with subsequent patients’ prognosis. Therefore, the goal of performing GTR for glioblastoma should be achieved when possible since it appears to increase NKA cell immunity.

Systemic and local immunosuppression in glioblastoma and its prognostic significance

“…In contrast to changes in the counts of T cell subsets, MDSCs, and neutrophils (discussed below), natural killer (NK) cells (45, 46,[76][77][78] and natural killer T (NKT) cells (79,80) were within the normal range in patients with glioblastoma/glioma before standard therapy in the majority of studies, although their cytotoxic activity may have been impaired (44,81,82).…”

Challenges and Perspectives of Neurological Disorders

“…The impaired NKA recovery was also associated with an increase in the CD56 bright CD16 - NK cell subset. Therefore, the study suggests that GTR may improve NKA and increase the CD56 bright CD16 - NK subset, which could be associated with subsequent patient prognosis, and should be performed when possible [ 11 ].…”