Phenotypic alterations in tumors that developed from threshold subcutaneous inocula. I. Reduced binding of natural antibodies and sensitivity to hypotonic lysis.

Tumors obtained from the injection site of threshold subcutaneous inocula of L5178Y-F9 or SL2-5 lymphomas in syngeneic mice exhibited increased tumor frequencies and reduced sensitivities to other parameters of natural immune resistance in vivo and in vitro. An examination of the resistant phenotype of cells derived through this model of tumor progression revealed that the more aggressive in vivo grown cells were less able to inhibit natural killer (NK) cell cytolysis and to bind natural antibodies (NAb) measured through fluorescence analysis, although they could not be distinguished from the starting clones by absorption of NAb for complement-mediated lysis. The in vivo grown cells also exhibited a reduced sensitivity to hypotonic lysis, which was not detectable after preincubation at 4 degrees C or upon exposure to sodium azide, procedures that reduced the lysis of the starting clones. The differential susceptibility of the in vivo grown cells was increased to control levels by treatment with cycloheximide or colchicine. These studies suggest that a decreased sensitivity to lysis associated with a reduced autolytic process and an increased counterlytic mechanism, in addition to a reduced antigen expression for binding of NK cells and certain NAb contribute to this resistant phenotype, which may characterize tumors that arise under the selective pressure of natural resistance mechanisms in the natural course of neoplastic development.