Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12).

A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 (51Cr) release assay.

Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2, GM-CSF, and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells.

PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of tumor subclones with limited antigenic spectra during retrovirus-mediated gene transfer.

Traumatic brain injury (TBI) is a concern of contemporary military deployments. Whether milder TBI leads to enduring impairment remains controversial.

To determine the influence of deployment TBI, and posttraumatic stress disorder (PTSD) and depression symptoms on neuropsychological and functional outcomes.

A sample of 760 US Army soldiers were assessed pre- and post-deployment. Outcomes included neuropsychological performances and subjective functional impairment.

In total, 9% of the participants reported (predominantly mild) TBI with loss of consciousness between pre- and post-deployment. At post-deployment, 17.6% of individuals with TBI screened positive for PTSD and 31.3% screened positive for depression. Before and after adjustment for psychiatric symptoms, TBI was significantly associated only with functional impairment. Both PTSD and depression symptoms adjusted for TBI were significantly associated with several neuropsychological performance deficits and functional impairment.

Milder TBI reported by deployed service members typically has limited lasting neuropsychological consequences; PTSD and depression are associated with more enduring cognitive compromise.