Host Defense Mechanisms Against Experimental Metastasis of Murine B16 Melanoma Using H-2 Loss Variant Cell Lines

Abstract

We have studied the host defense mechanisms against the experimental metastasis of B16 melanoma cells using H-2 loss variant cell lines. The NK cells revealed an appreciably higher killing activity toward H-2^- cells and prevented pulmonary metastasis of this H-2 loss variant compared to the H-2⁺ cells. The tumor bearing state using MMC-treated B16 H-2⁺ and H-2^- cells inhibited pulmonary metastasis of the corresponding B16 melanoma cells in NK and T cell-depleted host. In mixed lymphocyte-tumor cell culture (MLTC) experiments, B16 H-2^- cells induced non-specific killer cells such as lymphokine-activated killer (LAK) cells, and demonstrated the ability to kill a variety of tumor cells. Furthermore, the effector cells demonstrating broad specificity generated from the spleen cells in H-2^--bearing host by incubation for 6 days without IL-2 stimulation. These results thus suggest that the activated killer cells are generated from tumor bearing hosts and play a role against the metastasis of B16 melanoma cells with NK defense system. Considering that developing melanoma cells often have an alteration in the MHC molecule, it is important to better understand the mechanism involved in immunotherapy, particularly against the metastasis of melanoma cells.