Astrocytoma infiltrating lymphocytes include major T cell clonal expansions confined to the CD8 subset

Anaplastic astrocytoma and glioblastoma are frequent and malignant brain tu mors that are infiltrated by T lymphocytes, Whether these cells result from non-specific inflammation following blood-brain barrier disruption or an a ntigen-driven specific immune response is unknown. In this study, an in-dep th characterization of TCR diversity in tumor and blood RNA biopsies was pe rformed in a series of 16 patients with malignant astrocytoma, Whilst there was no obvious restriction of the AV and BV gene segment usage, complement arity-determining region 3 size analysis and sequencing of amplified TCR tr anscripts revealed multiple T cell oligoclonal expansions in ail astrocytom as analyzed. Unique T cell clones were present in different adjacent areas of a given tumor, but never detected in the blood. Quantification of the nu mber of TCR clonal transcripts per mu g of tumor RNA indicated that certain T cell clonal expansions may represent at least 300 cells/10(6) tumor cell s, Furthermore, we demonstrated that the in vivo expanded clones were almos t exclusively confined to the CD8(+) subset. Overall, these data suggest th at spontaneous antigen-driven immune responses may be elicited against huma n astrocytoma despite the immunosuppressive microenvironment generated by t he 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 T-h component of the response. This observation could have important conseq uences for the development of immunotherapies for astrocytoma patients.