The War Is on: The Immune System against Glioblastoma—How Can NK Cells Drive This Battle?

Abstract

Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptive transfer of in vitro expanded and activated cells, genetically engineered cells to contain chimeric antigen receptors (CAR-NKs), in vivo stimulation of NK cells (by cytokine therapy, checkpoint blockade therapies, etc.), and tumor-specific antibody-guided NK cells, among others. In this article, we review pivotal aspects of NK cells’ biology and their contribution to immune responses against tumors, as well as providing a wide perspective on the many antineoplastic strategies using NK cells. Finally, we also discuss those approaches that have the potential to control glioblastoma—a disease that, currently, causes inevitable death, usually in a short time after diagnosis.

The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment

“…This is in concert with the findings of Chongsathidkiet et al., who describe exceptionally low T cell numbers, especially of naive CD4+ T cells, due to T cell sequestration in the bone marrow ( 13 ). NK cells in glioblastoma are investigated in the context of immunosurveillance ( 19 , 20 ) or as a vehicle for therapy ( 21 , 22 ). However little is known about circulating NK cells in intracranial cancer.…”

Systemic and local immunosuppression in glioblastoma and its prognostic significance

“…NK cells and invariant NKT cells are scarcely present in glioblastoma/glioma tissue (60,183,184), and the role of these immune cell subtypes has not been clearly established in patients with glioblastoma/glioma. Nevertheless, there is increasing evidence of NK or NKT cell-based immunotherapy efficacy in rodent glioma models (197,198). In addition, a local administration of activated haploidentical NK cells (199) or irradiated CAR-NK cells (NK-92/ 5.28. z) targeting HER2 (200) in patients with recurrent glioblastoma was feasible and safe.…”

Natural killer cell-derived exosomes for cancer immunotherapy: innovative therapeutics art

“…In NK cell adoptively transferred strategies, diverse and innovative approaches are used for isolating, expanding, manipulating, or producing ex vivo activated autologous or allogeneic NK cells, which are administrated to patients to act against the tumor [ 57 ]. These cells are isolated or differentiated from multiple sources such as peripheral blood of patients or healthy donor, stem cells (induced pluripotent stem cells, human embryonic stem cells, or hematopoietic stem cells), and established human cell lines and then expanded with different methods to sufficient and large scale[ 58 , 59 ]. One of the challenges for successful NK cell therapy is the ability to obtain large numbers of cells from a limited number of NK cells from different sources [ 60 ].…”