Serotherapy of cancer: cellular changes in primary rat mammary carcinomas after infusion of syngeneic sera absorbed with protein A-Sepharose.
Serotherapy and plasma therapy have proved to be effective in the treatment of diverse neoplasms. The mechanisms of the tumoricidal or growth-inhibitory effects are unknown. We previously reported that activation of the alternative pathway of complement in absorbed sera correlated with the presence of anti-tumor activity. Complement components generated during absorption may serve as the initial mediators of cytotoxicity; for example, C5a may function in its role as a chemo-attractant. To further investigate the anti-tumor mechanisms, we undertook a series of sequential histological studies of in vivo changes in tumors following i.v. serotherapy. We found diffuse inflammatory cellular infiltrates in the interstitial compartments of primary mammary carcinomas of rats within 3-4 hr of administration of protein A-Sepharose absorbed syngeneic serum. The number of inflammatory cells was significantly higher in tumors from treated rats: total infiltrating cells (p = 0.002), eosinophils (p = 0.001), neutrophils (p = 0.001), macrophages (p = 0.001), lymphocytes (p = 0.004) and plasma cells (p = 0.001). Also, the mitotic index of tumor cells was significantly lower 4 hr after serotherapy when compared with that of untreated rat tumor cells. C3 in tumor tissue was decreased at 4 hr following serotherapy. Fibrosis was present in tumor nodules with retarded growth 5 weeks after the start of serotherapy. Localization of the infiltrating cells to tumor interstitial compartments prevents direct contact between inflammatory cells and neoplastic cells, making it unlikely that direct cell-cell killing occurs. Indirect cell killing within the tumor bed apparently occurs through several mechanisms involving interactions between serotherapy-initiated humoral mediators and inflammatory cells. The resulting anti-tumor effects include microvascular injury leading to localized ischemia, tumor infarction, and fibroblastic reactions obstructing tumor invasion and growth.
Glenn
G M
GM
Laboratory of Immunobiology, NCI-FCRF, Frederick, MD 21701.
Szende
B
B
Yano
T
T
Zbar
B
B
Borsos
T
T
D000818:Animals; D000906:Antibodies / Q000302:isolation & purification*; D001772:Blood Cell Count; D002846:Chromatography, Affinity; D003167:Complement Activation; D003176:Complement C3 / Q000032:analysis; D003182:Complement C5 / Q000276:immunology; D015936:Complement C5a; D003602:Cytotoxicity, Immunologic; D005260:Female; D007116:Immunization, Passive; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008770:Methylnitrosourea; D008940:Mitotic Index; D051381:Rats; D012685:Sepharose / Q000031:analogs & derivatives; D013205:Staphylococcal Protein A
D000906:Antibodies; D003176:Complement C3; D003182:Complement C5; D015936:Complement C5a; D008770:Methylnitrosourea; D012685:Sepharose; C042030:Staphylococcal protein A-sepharose; D013205:Staphylococcal Protein A