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Systematic Comparison of Dendritic Cell-based Immunotherapeutic Strategies for Malignant Gliomas: In Vitro Induction of Cytolytic and Natural Killer-like T Cells.


Posted on: 11/02/2004

Systematic Comparison of Dendritic Cell-based Immunotherapeutic Strategies for Malignant Gliomas: In Vitro Induction of Cytolytic and Natural Killer-like T Cells.

Neurosurgery. 2004 Nov;55(5):1194-1204.

Parajuli P, Mathupala S, Sloan AE.

Department of Neurosurgery, Wayne State University and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.

OBJECTIVE: To compare the efficacy of various immunotherapeutic strategies of loading dendritic cells (DCs) with whole-glioma cell antigens and characterize the effector responses induced.

METHODS: DCs were either fused with major histocompatibility complex (MHC)-matched glioma cells (Fusion) or pulsed with apoptotic tumor cells (DC/Apo), total tumor ribonucleic acid (RNA) (DC/RNA), or tumor lysate (DC/Lys). These tumor-DC preparations were then assessed for their phenotype, cytokine profile, and capacity to stimulate autologous peripheral blood mononuclear cells (PBMCs) in vitro. Phenotype and tumor-specific cytolytic activities of various effector cell populations were characterized and compared.

RESULTS: The various tumor-DC preparations exhibited similar phenotype and cytokine profiles irrespective of the method of loading tumor-cell antigens. However, the fusion, DC/Apo, and DC/RNA induced superior tumor cytolytic activities in PBMCs compared with DC/Lys or DC and tumor controls. DC/Apo induced the greatest expansion of tumor-specific lymphocytes, as detected by trypan blue exclusion and thymidine incorporation assays. Flow cytometric analyses also revealed the highest relative percentages of T helper cells (CD3(+)CD4(+)), cytotoxic T lymphocytes (CTLs) (CD3(+)CD8(+)), and natural killer (NK)-like T cells (CD3(+)CD56(+)) in the DC/Apo group among all the groups studied, indicating that DC/Apo induced expansion of PBMCs bearing multiple T and NK cell markers. Interestingly, isolated NK-like T cells demonstrated significantly higher tumor cytotoxicity compared with CTLs isolated from the same groups and was also non-MHC-restricted.

CONCLUSION: Apoptotic tumor cells may be an optimal source of whole-tumor-cell antigen for immunotherapy of gliomas. The study also demonstrates for the first time that both CTLs and NK-like T cells are expanded and stimulated by mature, tumor-pulsed DCs.

PMID: 15509326 [PubMed - as supplied by publisher]


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