Natural killer cell awakening: unleash cancer-immunity cycle against glioblastoma

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.