Defects in tumor cell immunogenicity: lymphokine signals in in vitro cytolytic responses to tumor alloantigens.
The B16 melanoma of C57BL/6 mice illustrates a deficiency in immunostimulation which may be important in some host-tumor relationships. B16 immunizes very poorly, even against its own major histocompatibility complex (MHC) antigens. We have compared the anti-MHC cytolytic response induced in vitro by B16 and by other tumors of both lymphoid and nonlymphoid origin. We have also studied the role of indomethacin and exogenous lymphokines in facilitating these responses and examined the relationship of specific and nonspecific effector cells induced. In contrast to normal lymphoid cells and two lymphoid tumor cells (EL4 and WEHI-265), the three nonlymphoid tumors, B16, Lewis lung tumor (3LL), and MC-2 fibrosarcoma, failed to induce primary cytolytic responses by themselves. MC-2 and B16 represented two different defects in immunogenicity. MC-2, which we have shown previously to induce an in vivo cytolytic response, could also immunize in vitro provided that prostaglandin production was blocked with indomethacin. In contrast B16, which is poorly immunogenic in vivo, immunized in vitro only if a concanavalin A-induced lymphokine supernatant (CS) was added as an exogenous source of "signal 2." High concentrations of the interleukin 2-containing Con A-induced spleen cell culture supernatant-induced non-H-2b-specific lymphokine-activated killer (LAK) cells in the absence of B16 stimulator cells. However, lymphokine concentrations too low to induce LAK cells enabled the otherwise nonimmunogenic B16 cells to induce specific cytolytic activity.
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008222:Lymphokines / Q000276:immunology* / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology*
D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D008222:Lymphokines; D007213:Indomethacin