DOMINANT-NEGATIVE P53 CAN RESTORE TUMORIGENICITY OF L-929 CELLS IN IMMUNOCOMPETENT MICE

To study the effect of a transforming allele of the tumor suppressor p53 upon the anti-tumor immune response, antigenic L-929 cells were transfected with the dominant-negative valine(135) mutant of murine p53. Several p53(val135)-expressing transfectants formed non-regressing tumors in immunocompetent hosts. The growth rates of tumorigenic and non-tumorigenic clones were equivalent in vitro in sublethally irradiated C3H/HeN mice and in nude mice. Tumorigenic and nontumorigenic p53(val135)-expressing L-929 clones expressed equivalent levels of cell surface class I major histocompatibility complex (MHC) glycoproteins. Immunization with a tumorigenic Lp53(val135) clone protected mice from subsequent challenge and primed MHC class I-restricted cytotoxic T-lymphocytic precursors. Secretion of an immunosuppressive cytokine, transforming growth factor beta-1 and sensitivity to tumor necrosis factor-ru were equivalent from tumorigenic and non-tumorigenic cell lines. These data suggest that expression of a transforming allele of p53 can allow L-929 cells to escape the host immune system. (C) 1995 Wiley-Liss, Inc.