Escape of TA3 tumors from allogeneic immune rejection: theory and experiments

Abstract

A factor promoting tumor growth in allogeneic mice was found in the ascites fluid of TA3-Ha tumor-bearing mice. Preliminary attempts t o isolate this factor resulted in a preparation (P3), devoid of free immunoglobulins or serum proteins, which had enhanced action in promoting tumor growth in vivo. Electron microscopy showed that the P3 preparation is of membranous origin. Biochemical assays for membrane marker enzymes were positive. 5'-Nucleotidase and alkaline a-glycerophosphatase activity was found. Chemical and gas-liquid chromatographic analysis of long-chain carboxylic acids present in the tumor cell membrane and in the P 3 revealed the presence of fatiy acids in almost identical ratios in both preparations, again indicating the membranous character of P3.The P3 preparation as well as the ascites fluid have immunogenic properties. They could induce immune tolerance if injected neonatally and the P3 preparation could immunize against the TA3-Ha tumor if injected intramuscularly or subcutaneously into adult mice. It had no effect if injected intravenous- A working hypothesis has been proposed according t o which TA3-Ha tumor cells produce highly reactive membranous decay products which intercept incoming immunocytes o r immunoglobulins before they can reach their targets o n living tumor cells. Whether this self protection of TA3 ascites tumors can be applied to other tumors remains t o be investigated.ly.

Rigid plasma‐membrane‐derived vesicles, enriched in tumour‐associated surface antigens (MLr), occurring in the ascites fluid of a murine leukaemia (GRSL)

“…The shedding of tumour antigens in general and the significance of this for the tumour immunity in the host has been described by many authors, reviewed by Doljanski andKapeller (1976), Nicolson (1976), and Price and Baldwin (1977). The spontaneous shedding of (antigen-containing) membrane fragments (vesicles) from viable cells has been reported by Vitetta and Uhr (1972), Nowotny et al (1974), De Broe et al (1977), and Koch and Smith (1978).…”

“…Part of the vesicles encountered in the GRSL ascites fluid and cell washes may be detached microvilli or other surface projections (Nowotny et al, 1974;Price and Baldwin, 1977;Koch and Smith, 1978). Direct evidence that budding off at the apical portion of microvilli may be a regular feature of the turnover of cells has been presented by Marcus (1962) and Koch and Smith (1978).…”

Temporal Synthesis and Presentation of Antigens by Cultured B16 Melanoma Cells

“…In view of those observations, a melanoma cell's ability to modulate its synthesis of antigens and to alter its presentation of the antigens in response to environmental conditions becomes significant. It is especially noteworthy that con-fluent cells shifted their total protein synthesis in favor of B700 and B50 antigen production, since the wholesale production and release of decoy antigens has been proposed as a method by which the tumor can subvert the host's immune responses (Gersten et al, 1981;Nowotny et al, 1974).…”

Comparative Study on Drug Sensitivity of the TA3/Ha and TA3/St Tumor Sublines

“…TA3 tumor lines are used for various purposes but most frequently for cell surface, immunological and immunogenetical studies [1][2][3][4][5][6][7][8][9][10][11][12][13]. These tumors, since the time of their spontaneous growth have been main tained only in isogenic hosts.…”