Increased sensitivity of tumor cells to immune defense cells following treatment with antineoplastic agents in vitro

Abstract

Murine EL-4 thymoma cells became highly sensitive to attack by cytotoxic T-lymphocytes (CTL) and allo-reactive T-cells in a 4-hr 51Cr release assay when the target EL-4 cells had been either incubated with 5-fluorouracil, cytosine arabinoside or hydroxyurea at 37 degrees C for 16 hr (nearly one generation period), or exposed for 30 min to adriamycin, actinomycin D, bleomycin, mitomycin C, 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitros our ea, cis-diamminedichloroplatinum(II) or 4-hydroperoxycyclophosphamide followed by incubation for 16 hr. In contrast, short-term exposure of EL-4 cells to the latter group of drugs had no effects on immune lysis in vitro. Target cells treated with these antineoplastic agents were enlarged in volume, resulting from the blockade of cell division, and the major histocompatibility complex (MHC) class I antigens detectable on the cell surface were significantly increased in the treated cells. CTL can lyse altered cells by recognizing foreign antigens in association with MHC class I antigens. Thus, these data suggest that the enhanced sensitivity of target tumor cells to CTL lysis following treatment with antineoplastic agents could be at least partly due to increases in the expression of MHC class I antigens. These treatments made natural killer (NK)-resistant EL-4 cells susceptible to NK lysis, hence, their relation to chemoimmunotherapy for cancer is discussed.