Soluble suppressor factors elaborated in experimental malignant ascites.
Soluble suppressor factors in the sera of cancer patients inhibit lectin-stimulated lymphocyte proliferation. These factors, derived from human material, preclude easy corroboration by other investigators. To gain a general understanding of soluble suppressor factors and to avoid the necessary restrictions of human experimentation, an animal model was devised. Sprague-Dawley rats were injected ip with the Walker 256 carcinoma. The resultant ascites proved to be a stable, reproducible source of soluble suppressor factors. Ascites inhibited phytohemagglutinin (PHA)-induced blastogenesis of normal splenocytes by 98%. The possibility of a toxic effect was eliminated by vital staining of splenocytes and by examination in a specific lymphotoxin assay. Suppressor activity persisted after heating at 100 degrees C for 40 min. Extraction by lipid solvents revealed that the bulk of suppressor activity resides in the lipid phase. The active fraction of heat-treated ascites passed through an Amicon PM-10 filter. Thin-layer chromatography revealed the presence of prostaglandins E2 and F2 alpha. Tissue culture supernatants from short-term cultures derived from tumor-bearing animals revealed suppressor activity from thymus, spleen, and liver cultures (97, 91, and 71%, respectively). No suppressor activity was detected in cultures of cancer cells. This study has demonstrated in this animal model that prostaglandins play a major role in suppression of lectin-induced blastogenesis. All suppressor factors appear to be host derived. An understanding of the mechanism of release of these suppressor substances may open new avenues in the immunotherapy of cancer.
D000818:Animals; D002279:Carcinoma 256, Walker / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D007165:Immunosuppression Therapy; D007739:L Cells / Q000187:drug effects; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D008233:Lymphotoxin-alpha