Induction of suppressor cells by a tumor-derived suppressor factor

Area of Science:

• Immunology
• Cancer Research
• Molecular Biology

Background:

• Murine fibrosarcomas can suppress immune responses.
• Delayed-type hypersensitivity (DTH) is a key cell-mediated immune response.
• Tumor-induced immunosuppression can facilitate cancer progression.

Purpose of the Study:

• To investigate the mechanism by which fibrosarcomas suppress DTH responses.
• To identify and characterize the immunosuppressive factor produced by fibrosarcomas.
• To determine the nature of the cells involved in mediating tumor-induced immunosuppression.

Main Methods:

• Partial purification of tumor-derived suppressor factor (TDSF) using preparative isoelectric focusing.
• Incubation of normal spleen cells with TDSF to induce suppressor cells.
• In vivo transfer of TDSF-treated spleen cells to assess DTH inhibition.
• Analysis of the efferent limb of the DTH response and characterization of involved cell populations (T cells, macrophages).
• Preliminary biochemical analysis of TDSF.

Main Results:

• A factor (TDSF) was identified in fibrosarcoma cultures and extracts that induces suppressor cells.
• These suppressor cells inhibit the DTH response to dinitrochlorobenzene (DNCB).
• TDSF activity was specific to fibrosarcomas and not found in normal cells.
• The suppressor cells act on the efferent limb of the DTH response.
• Biochemical analysis suggests TDSF is an RNA-protein complex.

Conclusions:

• Murine fibrosarcomas produce a soluble factor (TDSF) that activates splenic suppressor cells.
• TDSF inhibits immune responses to non-neoplastic antigens by suppressing the DTH response.
• These findings reveal a novel mechanism of tumor-induced immunosuppression involving ribonucleoprotein complexes.