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

Davidson DD, Carney DN, Putnam JB, Sugarbaker PH, Roth JA
J Surg Res. 1985 38 (3): 289-97

PMID: 2984465 · DOI:10.1016/0022-4804(85)90040-x

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 X A/J) F1 anti-B10. BR mixed lymphocyte reaction (MLR) was developed. Optimal [3H]Tdr incorporation was on Day 4 with 1 X 10(5) responders and 2 X 10(5) 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 X 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.

MeSH Terms (20)

Animals Carcinoma, Small Cell Cell Division Cell Line Colonic Neoplasms Culture Techniques Cytotoxicity, Immunologic Humans Immune Tolerance Liposarcoma Lung Neoplasms Lymphocyte Culture Test, Mixed Mice Mice, Inbred C3H Neoplasms Oxidation-Reduction Phytohemagglutinins Protein Denaturation Spleen Trypsin

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