Immunomodulation of host resistance by tumor variants.

Immunomodulation of host resistance by tumor cell variants has been investigated in the context of immunological effects of tumor cell heterogeneity using a murine tumor model. Clonal variation in the susceptibility to specific T cell-mediated cytotoxicity (TC), which is inversely related to tumorigenicity in syngeneic animals, was demonstrated among clones derived from a cultured line of DBA/2 lymphoma L1210 by limiting dilution. Thus, although a majority of such clones were TC-resistant and highly tumorigenic, some clones were TC-susceptible and non-tumorigenic. Moreover, an inoculation of the variant clones bearing the latter phenotype was shown to elicit protective immunity in host mice against a challenge with the parent L1210, whereas an inoculation of spleen cells (or extracts) from hosts bearing tumorigenic clones would abrogate the priming effects of the non-tumorigenic variants, presumably through splenic suppressor cells. These results suggest that heterogeneity among variant clones may influence the regulation of host resistance against tumors.