Analysis of Local Immunoresponses in Local Application of Various Effector Cells in a Rat Brain Tumor Model

Adoptive immunotherapy with lymphokine activated killer （LAK） cells and interleukin-2 （IL-2） has been shown to be an effective approach to treat cancer patients and for established tumors in animal models. However, the precise nature of local immune response induced by LAK cells at the brain tumor site remains to be determined. The purpose of this study was to; （1） evaluate the antitumor effects of LAK cells on experimental brain tumors and analyze local immune response at the tumor site, and （2） determine if different effector cells caused different immune reactions at the tumor site. Inbred 7-week old F344 rats were inoculated with 1×104 syngeneic gliosarcoma （T9） cells into the right basal ganglia. Ten days after inoculation, different immune effector cells （normal spleen cells, immune spleen cells, tumor infiltrating lymphocytes （TIL）, and LAK cells） were administered intratumorally using a Hamilton microsyringe apparatus. Normal spleen cells and immune spleen cells were found to be cytotoxic against only natural killer （NK）-sensitive target cells, whereas TIL showed cytotoxicity against only T9 cells in terms of 51Cr release assay. LAK cells showed strong cytotoxicity against NK-sensitive, NK-resistant, and T9 cells. Immunohistological analysis revealed a more intense accumulation of CD8-positive cells at the tumor site after injection of LAK cells than that of TIL, immune spleen cells, or normal spleen cells. The therapeutic effects of LAK cells on this brain tumor model was also statistically observed. These results suggested that LAK cells not only kill T9 tumors directly but also induce local immune response at the brain tumor site.departmental bulletin pape