Due to the negligence of the complex
tumor immune microenvironment, traditional treatment for
glioblastoma has reached its limitation and cannot achieve a satisfying outcome in the past decade. The emergence of
immunotherapy based on the theory of
cancer-immunity cycle has brought a new dawn to
glioblastoma patients. However, the results of most phase II and phase III clinical trials are not optimistic due to the simple focus on T cells activation rather than other immune cells involved in anti-
tumor immunity. NK cells play a critical role in both innate and adaptive immunity, having the ability to coordinate immune response in
inflammation,
autoimmune disease and
cancer. They are expected to cooperate with T cells to maximize the anti-
tumor immune effect and have great potential in treating
glioblastoma. Here, we describe the traditional treatment methods and current
immunotherapy strategies for
glioblastoma. Then, we list a microenvironment map and discuss the reasons for
glioblastoma inhibitory immunity from multiple perspectives. More importantly, we focus on the advantages of NK cells as potential immune regulatory cells and the ways to maximize their anti-
tumor immune effect. Finally, our outlook on the directions and potential applications of NK cell-based
therapy combining with the advance technologies is presented. This review depicts NK cell awakening as the precondition to unleash the
cancer-immunity cycle against
glioblastoma and elaborate this idea from biology to clinical treatment.