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

BACKGROUND: 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(+ )T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA) for over 12 years without recurrence. METHODS: 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(+ )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. RESULTS: The patient's tumor expressed both EphA2 and IL-13Rα2, and in vitro stimulated PBMC demonstrated superior EphA2(883–891 )and IL-13Rα2(345–353)-specific CTL reactivity compared to PBMC samples from two other patients with progressing malignant glioma. Unstimulated EphA2(883–891)-reactive CD8(+ )T cells contained high numbers of CD45RA(-)/CCR7(- )late effector and CD45RA(-)/CCR7(+ )central memory cells. Among other leukocyte subsets, elevated numbers of NK-T cells were found. CONCLUSION: To our knowledge, the current study is one of the first demonstrating the presence of antigen-experienced, GAA-reactive CD8(+ )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(+ )T cells dictates survival of patients and/or response to therapeutic vaccines.