Functional analysis of mononuclear cells infiltrating into tumors: differential cytotoxicity of mononuclear cells from tumors of immune and nonimmune rats.

A million syngeneic gliosarcoma (T-9) cells injected subcutaneously are sufficient to kill Fisher rats within 2 mo. Fisher rats became resistant to T-9 cells by surgical removal of the implanted tumor and repeated immunization with MMC-treated T-9 cells. Histopathologic studies revealed massive accumulation of mononuclear cells in tumor tissues of immune rats that were rejecting syngeneic T-9 tumors, whereas very few mononuclear cells were found in tumor tissues of nonimmune rats. Cell populations infiltrating into tumor tissues were identified by immunohistochemical techniques. Mononuclear cells found within the regressing tumors of immune rats were identified mostly to be T cells, and two-thirds of these T cells were OX-8 positive. In contrast, mononuclear cells found within the growing tumors of nonimmune rats were identified to be mixtures of macrophages and T cells, and very few OX-8 positive cells were found. Mononuclear cells were isolated from implanted T-9 tumors to determine whether mononuclear cells lysed T-9 cells specifically. Significant tumoricidal activity was seen when mononuclear cells from tumors of immune rats were used, whereas no detectable tumoricidal activity was observed with mononuclear cells from tumors of nonimmune rats. Winn assays confirmed in vitro 51Cr release assays by showing that tumors were rejected only when T-9 cells were implanted into normal Fisher rats along with mononuclear cells from tumors of immune rats.