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

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

Research output: Contribution to journalArticle

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 - 1985
Externally publishedYes

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Mixed Lymphocyte Culture Test
Neoplasms
Liposarcoma
Tissue Extracts
Small Cell Lung Carcinoma
Human Activities
Immunosuppression
Immune System
Colon
Cell Proliferation
Lymphocytes
Carcinoma
Muscles
In Vitro Techniques

ASJC Scopus subject areas

  • Surgery

Cite this

Suppression of murine immunologic functions by fresh and cultured human tumor extracts. / Davidson, Darrell; Carney, Desmond N.; Putnam, Joe B.; Sugarbaker, Paul H.; Roth, Jack A.

In: Journal of Surgical Research, Vol. 38, No. 3, 1985, p. 289-297.

Research output: Contribution to journalArticle

Davidson, Darrell ; Carney, Desmond N. ; Putnam, Joe B. ; Sugarbaker, Paul H. ; Roth, Jack A. / Suppression of murine immunologic functions by fresh and cultured human tumor extracts. In: Journal of Surgical Research. 1985 ; Vol. 38, No. 3. pp. 289-297.
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