Enhanced cell-mediated cytotoxicity by interferon-gamma and interleukin-2 against syngeneic murine mammary adenocarcinoma

Abstract

The effect of murine recombinant interferon-gamma (IFN-gamma) on cell-mediated cytotoxicity against tumor cells in vitro and in vivo was investigated using a spontaneously developed, weakly immunogenic, syngeneic murine mammary adenocarcinoma, designated JC, as the target. Preincubation of JC tumor cells with IFN-gamma increased the susceptibility of lysis by both cytotoxic T lymphocytes and interleukin-2 (IL-2)-induced lymphokine-activated killer cells in an IFN-gamma dose-dependent manner. A direct injection of IFN-gamma (10,0000 U/d) daily for 5 consecutive days into the JC tumor nodule on the backs of BALB/c mice reduced the tumor growth in comparison with that of the control group. This antitumor activity was further enhanced by combination with a simultaneous intraperitoneal injection of IL-2 (300,000 IU/d) daily for 5 consecutive days. Phenotypic examination of tumor-infiltrating lymphocytes after injection of IFN-gamma plus IL-1 revealed an increased percentage of the cells expressing asialo GM1, L3T4, and IL-2 receptors. Additionally, an enhanced expression of major histocompatibility complex class I molecules on the JC tumor cells was detected. These results indicated that a direct injection of IFN-gamma into the tumor accompanied with the administration of IL-2, by enhancing cell-mediated immunity of the hosts and expression of major histocompatibility complex class I antigens on target cells, will be of potential clinical value.