Tumor growth in vivo selects for resistance to tumor necrosis factor Journal Article


Authors: Lattime, E. C.; Stutman, O.
Article Title: Tumor growth in vivo selects for resistance to tumor necrosis factor
Abstract: The relationship between in vivo tumor growth and resistance to TNF in WEHI-164 cells has been examined. When a highly TNF-sensitive clone of WEHI-164 was grown in vivo in syngeneic mice it became resistant to rTNF such that a 4 to 5 log higher concentration of TNF was required to produce tumor lysis in vitro. When compared with an in vitro selected TNF-resistant variant, the in vivo selected line was significantly more tumorigenic. The resistant phenotype of both the in vivo and in vitro selected variants was stable in culture and both selected lines were also resistant to lysis by syngeneic spleen cells with natural cytotoxic activity. The parental clone and the two variants were equally sensitive to lysis by allo-CTL and expressed similar levels of MHC class I Ag. Resistance to TNF in the two variants was not a function of de novo production of TNF measured as supernatant TNF activity or TNF mRNA expression. These studies are the first to demonstrate that in vivo tumor growth results in resistance to TNF and therefore may have direct relevance to the efficacy of TNF in the treatment of human neoplasms.
Keywords: nonhuman; animal cell; mouse; phenotype; animal; mice; cell division; cell line; animal experiment; mice, inbred balb c; mice, inbred c57bl; fibrosarcoma; cell culture; t-lymphocytes, cytotoxic; histocompatibility antigens class i; killer cells, natural; tumor growth; clone cells; therapy; tumor necrosis factor; sarcoma, experimental; immunity, natural; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Journal of Immunology
Volume: 143
Issue: 12
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 1989-12-15
Start Page: 4317
End Page: 4323
Language: English
PUBMED: 2592776
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 14 April 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Osias   Stutman
    45 Stutman
  2. Edmund C. Lattime
    18 Lattime