Faculty Bibliography

Optimal management of pineal region tumors depends on securing an accurate histologic diagnosis to facilitate management customized to the nuances of specific pathologies. As an initial step, surgical intervention by either stereotactic biopsy or open surgery is necessary to obtain tissue for pathologic examination. Stereotactic biopsy has the benefit of relative ease and minimal morbidity but is associated with greater likelihood of diagnostic inaccuracy compared to open surgery where more extensive tissue sampling is possible. The role of surgical debulking in the management of pineal tumors is clearly defined for some tumors but is less evident for others. Among the one third of pineal tumors that are benign or low grade, complete surgical resection is achievable and constitutes optimal management with excellent long-term recurrence-free survival. The benefits of aggressive surgical resection among malignant tumors are less clear but several studies have correlated degree of tumor removal with improved outcome. Advances in technology, surgical technique, and post-operative care have minimized surgical complications, however all surgical procedures in the pineal region, including both stereotactic biopsy and open surgery, are potentially hazardous. Advanced judgment, experience, and expertise are necessary to achieve rates of success sufficient to justify aggressive management. Management strategies using stereotactic biopsy, endoscopy, and radiosurgery can also provide favorable outcomes in some cases. Selective incorporation of these innovations can be expected to improve the already highly favorable outcome for all pineal region tumors.

OBJECTIVES: Adjuvant-linked vaccines have been shown to induce anti-tumor immunity in patients with a variety of solid tumors. In this study we describe an in vitro model of active immunotherapy using autologous fibroblasts as immunogen. Correlative results from glioma patients immunized with autologous fibroblasts are also described. METHODS: Peripheral blood lymphocytes (PBLs) from normal subjects were immunized in vitro against autologous skin fibroblasts coupled to the adjuvant muramyl dipeptide. The lymphocytes developed cell-mediated cytotoxicity that was measured with a short-term chromium release assay. Results of in vitro experiments were compared to data derived from glioma patients immunized with subcutaneous injection of an autologous adjuvant-linked fibroblast vaccine. Glioma target cells and fibroblast immunogens were derived from early passage primary tissue culture. RESULTS: A comparison of autologous vs. homologous immunogen indicated that major histocompatibility complex matching was required at the sensitization stage of immunity (17.2 +/- 3.4% specific lysis vs. 0.4 +/- 3.1%, P < 0.01). Pre-treatment of fibroblast immunogen cells with interferon gamma (IFN-gamma) was found to significantly increase immunity (42.2 +/- 10.0%, P < 0.01), as did IFN-gamma pre-treatment of tumor target cells (35.8 +/- 9.0%, P < 0.01). The positive effect of IFN-gamma was diminished by treatment of cells with IFN-alpha. These in vitro results correlated well with in vivo data derived from glioma patients immunized with an autologous adjuvant-linked fibroblast vaccine. PBLs from patients developed direct cell-mediated cytotoxicity against autologous tumor cells. Lysis of tumor targets after in vivo immunization increased over a three-week interval (from 1.2 +/- 3.0% to 21.0 +/- 3.4%, P < 0.01) while lysis of a non-MHC matched control cell line remained essentially unchanged. CONCLUSIONS: Specific lysis of glioma targets in vitro was achieved after in vivo sensitization with autologous adjuvant-linked fibroblasts. Collectively, the data indicate that biochemically modified autologous cells can stimulate anti-glioma immunity in humans. The degree of specific immunity seen in our patients compares favorably with other published series using glioma cells as an antigenic source. Accordingly, fibroblasts may represent a practical alternative to glioma cells for vaccine construction.