ABSTRACT
The purpose of the present research was to study immunity in the course of complex treatment for malignant gliomas of the brain and to evaluate extracorporeal antigen-specific immunotherapy (EASIT), a pilot procedure which was carried out according to an approved protocol. Initially, lowered HLA-DR+ monocyte count and in vitro inhibition of proliferative activity were reported in all patients. Inductive EASIT started in early postoperative period aborted immune disturbances caused by surgery. In 1998-2000, the procedure was performed in 33 patients with anaplastic astrocytoma (AA) (20) and glioblastoma (GB) (13). Mean dose of cell infusion was 2.43(0.18 x 109/patient and was well tolerated. There are 22 survivors and 9 patients died (GB--4 and AA--5; overall mortality--29%). Mean relapse-free survival was 14.2 mo (22); stable remission during 12-18 mo--37.5% (3/8)(GB) and 64% (9/14) (AA) Complete rehabilitation of immunity was generally reported 12 mo after the course of EASIT. Hence, complex treatment (surgery + EASIT) enhanced its efficacy in the management of brain tumors.
Subject(s)
Antigens, Neoplasm/immunology , Brain Neoplasms/immunology , Brain Neoplasms/therapy , Immunotherapy/methods , Adult , Astrocytoma/immunology , Astrocytoma/therapy , Brain Neoplasms/surgery , Combined Modality Therapy , Female , Glioblastoma/immunology , Glioblastoma/therapy , Humans , Male , Middle Aged , Pilot Projects , Treatment OutcomeABSTRACT
The investigation was concerned with assaying immunity and evaluating the role played by monocytes and tumor cells in the formation of T-cell dysfunction in malignant glioma (MG). The study group included 28 patients with anaplastic astrocytomas (n = 18) and glioblastomas (n = 10). MG patients showed significant changes in the numbers of CD16+ NK-cells and HLA-DR monocytes as well as lowered levels of HLA-DR expression on monocytes and proliferative response of T-lymphocytes as compared with both standard and alternative pathways of activation. Monocytes and macrophages suppressed T-cell activity due to production of prostaglandins E2 in such patients. Enhanced immunosuppression was also reported in 24-hour supernatants of tumor cells. Immune disorders were shown to involve apoptosis-independent mechanisms. Hence, despite the immune privilege of the brain, immunocompetent cells crossed blood-brain barrier and counteracted with tumor cells. As a consequence, monocyte function and cellular cooperation dropped while production of immunosuppressive factors rose, and T-cell dysfunction was brought about through apoptosis-independent mechanisms.
