NK Cells Recognize and Kill Human Glioblastoma Cells with Stem Cell-Like Properties

Abstract

In this study, cancer cells were isolated from tumor specimens of nine glioblastoma patients. Glioblastoma cells, cultured under suitable culture conditions, displayed markers typical of neural stem cells, were capable of partial multilineage differentiation in vitro, and gave origin to infiltrating tumors when orthotopically injected in NOD/SCID mice. These cells, although resistant to freshly isolated NK cells, were highly susceptible to lysis mediated by both allogeneic and autologous IL-2 (or IL-15)-activated NK cells. Indeed, all stem cellcultured glioblastoma cells analyzed did not express protective amounts of HLA class I molecules, while expressing various ligands of activating NK receptors that triggered optimal NK cell cytotoxicity. Importantly, glioblastoma stem cells expressed high levels of PVR and Nectin-2, the ligands of DNAM-1-activating NK receptor.

NK cells control breast cancer and related cancer stem cell hematological spread

“…These observations are in agreement with those previously reported in other human solid tumor experimental systems. [15][16][17]25 In Fig. 2, NK cells were activated with IL2 in vitro, whereas autologous and allogeneic NK cells were used as effectors without any activation in Table 1.…”

“…The low levels of MHC class I expression reported in CSCs hints at the low efficiency of CSC targeting by CD8 C T lymphocytes. 14,15 However, the expression of ligands for NK-activating receptors (NKG2D, NCR and DNAM-1) [15][16][17] points to NK cells and other innate immunity effector cells being able to recognize and eliminate CSCs. Indeed, recent data have demonstrated that human gd T cells can target CSCs in vitro.…”

“…20 NK cell tolerance is maintained by the engagement of inhibitory receptors which principally recognize MHC class I molecules (KIRs in humans, Ly49 receptors in mice). 21 Previous data have shown that NK cells selectively kill CSCs derived from human colon carcinoma, 15 melanoma 16 and glioblastoma, 17 in mainly in vitro experiments. We herein describe in vitro and in vivo experiments which validate the NK cell targeting of breast tumor-derived CSCs using CSC-enriched tumorspheres 22 derived from an ErbB-2 C murine breast cancer tumor cell line (TUBO), 23 and murine and human triple negative breast cancer (TNBC) cell lines.…”

The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes

“…In an autologous setting, normal cells are spared from NK-mediated killing because of the expression of high (protective) amounts of self-HLA class I molecules and of the lack of (or low) expression of ligands for activating NK receptors. However, tumors become susceptible to killing mediated by autologous NK cells because of a defective (nonprotective) expression of HLA class I molecules and de novo expression or up-regulation of ligands for activating NK receptors (6,7,9,11,12).…”

“…Different cellular ligands have been identified (5). DNAM-1 recognizes PVR and Nectin-2, two Nectin family members that are overexpressed in tumors (6,7), and NKG2D interacts with MICA/B and ULBP. 2B4 interacts with CD48, NKp80 recognizes the activationinduced C-type lectin (AICL) (8), and NTBA displays homophilic interaction.…”