The immunosuppressive state of a tumor-bearing patient is possibly mediated by tumor-derived factor. In this study, the authors characterized lung squamous cell carcinoma-derived immunosuppressive factor (LSCF). The immunosuppressive activity of QG56 (a lung squamous carcinoma cell line)-derived LSCF was evaluated by the effect of culture supernatant of QG56 on anti-CD3 monoclonal antibody-induced T-cell, response such as proliferation (3H-thymidine uptake), cytotoxicity (51Cr-releasing assay), and expression of cytokine mRNA (polymerase chain reaction). The LSCF was partially purified with an ion-exchange high-performance liquid chromatography (HPLC) and a gel-filtration HPLC. The LSCF inhibited proliferation, cytotoxicity, and expression of cytokine mRNA of T-cells in a dose-dependent manner. It has a molecular weight of approximately 22 kd, and was sensitive to proteinase K, heating at 60 degrees C, and resistant to treatment with trypsin and pH 3 and 9. These properties appear to be similar to those of transforming growth factor-beta (TGF-beta). However, the activity of the LSCF was not abrogated by anti-TGF-beta sera, and the LSCF did not suppress the proliferation of TGF-beta-sensitive mink lung cells (Mv1Lu). These data suggest that LSCF may be a novel tumor-derived immunosuppressive protein factor.