Suppression of murine immunologic functions by fresh and cultured human tumor extracts

Darrell D. Davidson, Desmond N. Carney, Joe B. Putnam, Paul H. Sugarbaker, Jack A. Roth

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Abstract

The role of human tumor-derived immunoregulatory factors (IRF) in the suppression of murine in vitro cell-mediated immune systems was investigated. IRF was extracted from a fresh human colon carcinoma and a liposarcoma using 3 M KCl. These extracts have previously been shown to suppress in vitro human immune responses. Both IRF extracts inhibited PHA-stimulated murine splenocyte [3H]Tdr uptake in a dose-dependent manner while extracts of normal tissue were not inhibitory. To further investigate in vitro immunosuppression a (C57BL/6 × A/J) F1 anti-B10.BR mixed lymphocyte reaction (MLR) was developed. Optimal [3H]Tdr incorporation was on Day 4 with 1 × 105 responders and 2 × 105 irradiated stimulators. Addition of IRF caused a 56% inhibition of this response but did not alter the kinetics of the MLR response. Induction of cell-mediated cytotoxicity (C57BL/6 × A/J F1 vs B10.D2) was significantly inhibited by addition of IRF during in vitro sensitization. Release of 51Cr from P-815 targets was decreased to spontaneous release levels at an effector:target (E:T) ratio of 20:1 when IRF was present during sensitization. At this E:T ratio, cells sensitized in the presence of a normal muscle 3 M KCl extract or medium caused 71 and 60% 51Cr release, respectively. IRF activity could also reproducibly be extracted from two small cell lung carcinoma tissue culture lines grown under a variety of culture conditions or passaged in nu/nu mice. The biochemical characteristics of the factor inhibiting human and murine lymphoid cell proliferation were identical. Thus, this system provides a convenient model for assessing the activity of human tumor-derived immunoregulatory factors.

Original languageEnglish (US)
Pages (from-to)289-297
Number of pages9
JournalJournal of Surgical Research
Volume38
Issue number3
DOIs
StatePublished - Mar 1985

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ASJC Scopus subject areas

  • Surgery

Cite this

Davidson, D. D., Carney, D. N., Putnam, J. B., Sugarbaker, P. H., & Roth, J. A. (1985). Suppression of murine immunologic functions by fresh and cultured human tumor extracts. Journal of Surgical Research, 38(3), 289-297. https://doi.org/10.1016/0022-4804(85)90040-X