Suppression of murine immunologic functions by fresh and cultured human tumor extracts.
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.
Davidson
D D
DD
Carney
D N
DN
Putnam
J B
JB
Sugarbaker
P H
PH
Roth
J A
JA
D000818:Animals; D018288:Carcinoma, Small Cell / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology; D046508:Culture Techniques; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007108:Immune Tolerance; D008080:Liposarcoma / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000276:immunology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011489:Protein Denaturation / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D014357:Trypsin
D010835:Phytohemagglutinins; D014357:Trypsin