A serpin from human tumor cells with direct lymphoid immunomodulatory activity: mitogenic stimulation of human tumor-infiltrating lymphocytes

Abstract

A serum-free supernatant from an epidermal carcinoma cell line has previously been shown to contain mitogenic activity for human tumor infiltrating lymphocytes in culture [1]. From this conditioned medium we have now purified to homogeneity, as determined by SDS-PAGE analysis, a ca. 45 kDa protein which stimulates [³H]thymidine incorporation into the DNA of these human T-lymphocytes. Amino acid composition data and immunoreactivity of the purified protein as well as sequence analyses of 7 tryptic fragments obtained therefrom suggest a strong similarity with human monocyte/neutrophil elastase inhibitor, which is a member of the serine protease inhibitor (serpin) superfamily. We have previously identified and purified from the same conditioned medium a 36 kDa protein with myeloid immunomodulatory activity [2]. Taken together, these two reports support the role of tumor-derived soluble factors in tumor immunosurveillance.