Relationship between cell-mediated and humoral immune attack on tumor cells: II. The role of cellular lipid metabolism and cell surface charge in the outcome of immune attack

Abstract

Treatment of P815 tumor cells with adriamycin increased their sensitivity to killing by anti-P815 antibody plus C, but not by allogeneic P815-sensitized spleen cells. Conversely, mitomycin C treatment enhanced the cells' sensitivity to cell-mediated, but not antibody-C, killing. Hydrocortisone, but not epinephrine, was effective in increasing the resistance of the cells to killing by both antibody-C and cell-mediated attack systems. The ability of the tumor cells to resist antibody-C killing correlated with their ability to incorporate fatty acid into complex cellular lipid; no such correlation was found between the cellular lipid synthesis and tumor cell susceptibility to cell-mediated killing. Drug or hormone-treated tumor cells exhibited unique changes in cellular lipid synthesis and composition and in cell surface physical properties that correlated with their susceptibility to antibody-C or cell-mediated attack. Cells increased in their sensitivity to antibody-C killing exhibited a decreased cholesterol:phospholipid mole ratio. In contrast, cells rendered more sensitive to cell-mediated killing exhibited an increase in polar phospholipid content and a measurable decrease in net negative cell surface charge density. These data implicate unique chemical and/or physical properties of tumor cells to be of fundamental importance for their ability to resist either humoral or cell-mediated immunologic attack; modulation of one or another of these cellular properties results in a change in the cells' susceptibility to immune killing by antibody plus C or by cytotoxic T lymphocytes.