Treatment > Immunotherapy

Meeting Abstract

Invariant natural killer T cells are preserved in patients with glioma and exhibit anti-tumor lytic activity

K. M. Dhodapkar, B. Cirignano, J. L. Finlay, R. M. Steinman

Rockefeller University, New York, NY; NYU Medical Center, New York, NY

Patients with high grade glioma have limited survival.
Prior studies to harness immune system have focused on T or natural killer (NK) cells, however it has proven difficult to reliably elicit anti-tumor lytic effectors.
Invariant natural killer T (NKT) cells are innate lymphocytes that recognize glycolipid ligands in the context of CD1d molecules.
Defects in NKT cells have been reported in patients with advanced cancer.
However in glioma, the tumor grows in an immune privileged site, without distant metastases.
We examined the NKT cell population in peripheral blood of patients with glioma (n=9).
8/9 patients were newly diagnosed and 5/9 had high grade tumor.
NKT cells were detectable in all patients examined (mean +/- SD: 0.07% +/- 0.06%) and were comparable to healthy controls (0.12% +/- 0.2%, p=0.2).
The cells were functional and secreted interferon-Γ (IFN-Γ) in response to stimulation with a synthetic NKT ligand Α-galactosylceramide (Α-GalCer), as measured in an elispot assay.
The number of ligand reactive IFN-Γproducing cells were comparable in both the patients and healthy controls (mean 84 vs 106 /million PBMCs; p=0.7).
No switch to ligand reactive IL-4 producing cells was seen in glioma patients.
NKT cells could be expanded in all patients using mature DCs loaded with Α-GalCer as antigen presenting cells to levels (mean frequency post-expansion 12.5 %), comparable to those previously observed in healthy donors.
The expanded cells secreted IFN-Γ in response to stimulation with PMA/Ionomycin.
Importantly, the expanded NKT cells were able to lyse glioblastoma (GBM) cell lines in a 51Cr release assay.
The lysis of the GBM cell lines was CD1d dependent and could be blocked by pretreating the targets with anti-CD1d antibody.
These data demonstrate that in contrast to reports in systemic cancer, NKT cell population is preserved in patients with glioma and has a Th1 phenotype.
These cells can be reliably recruited to effect anti-tumor activity using Α-GalCer loaded autologous mature DCs, providing a novel and distinct strategy for immunotherapy of human glioma involving transfer of NKT cells or immunization with Α-GalCer loaded DCs.

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