Mechanisms of immunosuppression in tumor-bearing mice: a multifactorial analysis.
Neoplastic growth results not only from the inherent proliferative potential of the neoplasm, but also from the neoplasm's ability to survive within a host whose immune responses may be activated to destroy it. It has been proposed that several mechanisms enable a neoplasm to outgrow the host. The present work describes a system for probing tumor-associated immunosuppression by utilization of the delayed hypersensitivity response to dinitrochlorobenzene (DNCB). Mice of the Balb/c and C3H/HeJ strains were sensitized with a subcutaneous injection of 2 mg DNCB followed 5-10 days later by the subcutaneous injection of a 0.05 mg challenge dose of DNCB in the hind footpad. The footpad response measured 24 hours after challenge is a delayed hypersensitivity reaction by virtue of the histology and kinetics of that response and because it is transferred by spleen cells but not by serum. DNCB sensitization is inhibited by spontaneous, chemical- and virus-induced syngeneic tumors in Balb/c and C3H/HeJ mice. Three mechanisms of immunosuppression are elucidated in the present experiments: (1) serum from tumor-bearing mice inhibits primary sensitization of normal mice to DNCB upon passive transfer; (2) spleen cells from tumor-bearing mice inhibit primary sensitization of normal mice to DNCB and appear to be macrophages in the C3H/HeJ system; and (3) an alteration of lymphocyte migration patterns exists in tumor-bearing mice that removes effector cells from the blood and prevents the initiation of a footpad response. The interrelationships of these three mechanisms are discussed. Correlations are also made with tumor-associated immunosuppression observed in cancer patients.
D000818:Animals; D004137:Dinitrochlorobenzene / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007111:Immunity, Cellular; D007114:Immunization; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009578:Nitrobenzenes / Q000276:immunology*; D012882:Skin Tests
D004137:Dinitrochlorobenzene; D009578:Nitrobenzenes