International Immunology, Vol. 11, No. 8, 1337-1350,
August 1999
© 1999 Japanese Society for Immunology
Astrocytoma infiltrating lymphocytes include major T cell clonal expansions confined to the CD8 subset
1 Laboratory of Tumor Immunology, Division of Oncology,
2 Transplantation Immunology Unit, and
3 Department of Neurosurgery, University Hospital, 1211 Geneva 14, Switzerland
4 Unit of Molecular Biology of the Gene, INSERM Unit 277, Department of Immunology, Pasteur Institute, 75724 Paris Cedex 15, France
5 Centre d'Immunologie Pierre Fabre, 74164 Saint-Julien-en-Genevois, France
Correspondence to: P.-Y. Dietrich
Anaplastic astrocytoma and glioblastoma are frequent and malignant brain tumors that are infiltrated by T lymphocytes. Whether these cells result from non-specific inflammation following blood–brain barrier disruption or an antigen-driven specific immune response is unknown. In this study, an in-depth characterization of TCR diversity in tumor and blood RNA biopsies was performed in a series of 16 patients with malignant astrocytoma. Whilst there was no obvious restriction of the AV and BV gene segment usage, complementarity-determining region 3 size analysis and sequencing of amplified TCR transcripts revealed multiple T cell oligoclonal expansions in all astrocytomas analyzed. Unique T cell clones were present in different adjacent areas of a given tumor, but never detected in the blood. Quantification of the number of TCR clonal transcripts per µg of tumor RNA indicated that certain T cell clonal expansions may represent at least 300 cells/106 tumor cells. Furthermore, we demonstrated that the in vivo expanded clones were almost exclusively confined to the CD8+ subset. Overall, these data suggest that spontaneous antigen-driven immune responses may be elicited against human astrocytoma despite the immunosuppressive microenvironment generated by the brain and the tumor itself. However, the ultimate failure of the immune system to control tumor growth could be the consequence of a deficient CD4 Th component of the response. This observation could have important consequences for the development of immunotherapies for astrocytoma patients.
Keywords: brain, TCR, T lymphocytes, tumor immunity
The last two authors share senior authorship
Transmitting editor: H. Robson MacDonald
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