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Soluble factors from murine and human tumors induce suppressor cells
Abstract:
A tumor-derived suppressor factor ( TDSF ) has been isolated from 3 M KCl extracts of a chemically induced fibrosarcoma of C3H/HeJ mice by preparative isoelectric focusing. Incubation of TDSF with normal spleen cells induces suppressor cells that enhance tumor growth and inhibit DTH to the chemical sensitizer 2,4-dinitro-1-chlorobenzene (DNCB). Similar suppressogenic activity has been detected in extracts of the 10T1/2 fibroblast line, an ultraviolet-induced fibrosarcoma of C3H/HeN mice, the C57B1/6J Lewis lung carcinoma, and four human colonic adenocarcinoma. TDSF activity was not found in extracts of syngeneic muscle or spleen cells. Chemical characterization of TDSF from the murine fibrosarcoma MCA-F revealed sensitivity to treatment with heat and RNase, partial sensitivity to treatment with trypsin, but resistance to treatment with DNase, pronase, and neuraminidase. TDSF has an apparent molecular weight of greater than 300 kDa by high-performance gel permeation chromatography. Acidic soluble factors isolated from murine and human tumors induce suppressor cells to inhibit cell-mediated immunity in an intact host.
Insights
Tumor-derived suppressor factor (TDSF) isolated from mouse fibrosarcoma enhances tumor growth by inducing suppressor cells. This factor inhibits cell-mediated immunity in mice and humans, impacting cancer progression.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Tumor-derived suppressor factor (TDSF) plays a role in immune evasion.
- Understanding TDSF's mechanism is crucial for cancer therapy.
Purpose of the Study:
- To isolate and characterize TDSF from murine fibrosarcoma.
- To investigate TDSF's effect on immune cells and tumor growth.
Main Methods:
- Preparative isoelectric focusing to isolate TDSF.
- Incubation of TDSF with normal spleen cells.
- Chemical characterization including heat, RNase, trypsin, DNase, pronase, and neuraminidase treatments.
- High-performance gel permeation chromatography for molecular weight determination.
Main Results:
- TDSF isolated from murine fibrosarcoma enhances tumor growth and inhibits delayed-type hypersensitivity (DTH).
- Suppressogenic activity detected in various murine and human tumor extracts, but not in normal cells.
- TDSF is sensitive to heat and RNase, partially sensitive to trypsin, and resistant to DNase, pronase, and neuraminidase.
- Apparent molecular weight of TDSF is >300 kDa.
Conclusions:
- Acidic soluble factors from tumors induce suppressor cells that inhibit cell-mediated immunity.
- TDSF represents a significant factor in tumor-induced immunosuppression.
- Further research into TDSF could lead to novel cancer treatment strategies.