This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tang, J. Articles by Andrews, D. W. Search for Related Content PubMed PubMed Citation Articles by Tang, J. Articles by Andrews, D. W.

Glioblastoma Patients Exhibit Circulating Tumor-Specific CD8+ T Cells

Authors' Affiliations: Departments of ¹ Neurosurgery, ² Medicine, and ³ Pathology, and ⁴ Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania

Requests for reprints: Phyllis Flomenberg, Infectious Disease, Thomas Jefferson University, Room 329, 1020 Locust Street, Philadelphia, PA 19107. Phone: 215-503-2170; Fax: 215-923-1956; E-mail: phyllis.flomenberg{at}mail.tju.edu.

Purpose: There is growing interest in developing cellular immune therapies for glioblastoma multiforme, but little is known about tumor-specific T-cell responses. A glioblastoma multiforme–specific T-cell assay was developed using monocyte-derived dendritic cells to present tumor antigens from the established glioblastoma multiforme cell line U118.

Experimental Design: Peripheral blood mononuclear cells (PBMC) and tumor cells were obtained from nine patients with newly diagnosed brain tumors: five glioblastoma multiforme, two oligodendroglioma, one ependymoma, and one astrocytoma. PBMCs were incubated overnight with autologous tumor cells or autologous dendritic cells loaded with a U118 cell lysate, and responses were detected by IFN- ELISPOT and cytokine flow cytometry assays.

Results: PBMCs from all glioblastoma multiforme patients exhibited IFN- responses to autologous tumor but not to HLA-mismatched U118 cells. Glioblastoma multiforme–specific IFN- responses were primarily mediated by CD8+ T cells and represented 2% of total CD8+ T cells. Additionally, all glioblastoma multiforme patients responded to autologous dendritic cells loaded with U118 lysate but not with low-grade astrocytoma cell lysates. PBMCs from four patients with other brain tumor types and one normal donor failed to respond to U118 lysate–loaded autologous dendritic cells. These data indicate that the IFN- responses to U118 lysate–loaded autologous dendritic cells are glioblastoma multiforme specific. Moreover, PBMCs stimulated 1 to 2 weeks with U118 lysate–loaded dendritic cells exhibited MHC class I–restricted cytotoxicity against autologous tumor cells.

Conclusions: Glioblastoma multiforme patients exhibit circulating tumor-specific CD8+ T cells that recognize shared tumor antigens from the glioblastoma multiforme cell line U118. These data show that glioblastoma multiformes are immunogenic and support the development of immunotherapy trials.

This article has been cited by other articles:

				S. De Vleeschouwer, S. Fieuws, S. Rutkowski, F. Van Calenbergh, J. Van Loon, J. Goffin, R. Sciot, G. Wilms, P. Demaerel, M. Warmuth-Metz, et al. Postoperative Adjuvant Dendritic Cell-Based Immunotherapy in Patients with Relapsed Glioblastoma Multiforme Clin. Cancer Res., May 15, 2008; 14(10): 3098 - 3104. [Abstract] [Full Text] [PDF]

				J. Tang, M. Murtadha, M. Schnell, L. C. Eisenlohr, J. Hooper, and P. Flomenberg Human T-cell responses to vaccinia virus envelope proteins. J. Virol., October 1, 2006; 80(20): 10010 - 10020. [Abstract] [Full Text] [PDF]