Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma

<p>Abstract</p> <p>Background</p> <p>In patients with high grade glioma, little is known regarding existence of naturally occurring adaptive T cell reactivity against glioma-associated antigens (GAAs). In this report, we characterized GAA-specific CD8<sup>+ </s...

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Bibliographic Details
Main Authors: Fujita Mitsugu, Zhu Xinmei, Low Keri L, Ueda Ryo, Sasaki Kotaro, Whiteside Theresa L, Butterfield Lisa H, Okada Hideho
Format: Article
Language:English
Published: BMC 2007-12-01
Series:Journal of Translational Medicine
Online Access:http://www.translational-medicine.com/content/5/1/68
Description
Summary:<p>Abstract</p> <p>Background</p> <p>In patients with high grade glioma, little is known regarding existence of naturally occurring adaptive T cell reactivity against glioma-associated antigens (GAAs). In this report, we characterized GAA-specific CD8<sup>+ </sup>T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA) for over 12 years without recurrence.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMCs) derived from the long term survivor with AA were evaluated for the frequency, cytotoxic T lymphocyte (CTL) activity and differentiation status of CD8<sup>+ </sup>cells recognizing GAA-derived epitopes as well as relative numbers of other immune cell subsets. This patient's AA tissue was evaluated for expression of two GAAs EphA2 and interleukin-13 receptor α2 subunit (IL-13Rα2) by immunohistochemistry.</p> <p>Results</p> <p>The patient's tumor expressed both EphA2 and IL-13Rα2, and <it>in vitro </it>stimulated PBMC demonstrated superior EphA2<sub>883–891 </sub>and IL-13Rα2<sub>345–353</sub>-specific CTL reactivity compared to PBMC samples from two other patients with progressing malignant glioma. Unstimulated EphA2<sub>883–891</sub>-reactive CD8<sup>+ </sup>T cells contained high numbers of CD45RA<sup>-</sup>/CCR7<sup>- </sup>late effector and CD45RA<sup>-</sup>/CCR7<sup>+ </sup>central memory cells. Among other leukocyte subsets, elevated numbers of NK-T cells were found.</p> <p>Conclusion</p> <p>To our knowledge, the current study is one of the first demonstrating the presence of antigen-experienced, GAA-reactive CD8<sup>+ </sup>T cells in a patient who has survived with AA for over 12 years without recurrence. Further studies are warranted to determine whether the status of GAA-reactive CD8<sup>+ </sup>T cells dictates survival of patients and/or response to therapeutic vaccines.</p>
ISSN:1479-5876