TUMOR-DERIVED SOLUBLE IMMUNOREGULATORY FACTOR

该项目旨在探索可溶性 肿瘤起源的免疫调节因子。 结果发现， 至少有四种经过辐照的培养的人类肿瘤细胞系， 刺激人淋巴细胞的增殖;观察到的 增殖刺激是由于分泌因子的活性， 存在于无血清肿瘤细胞上清液中（PNAS 87：4058-62，1990）。 此外，该上清液现在已被证明可以抑制 三种人白血病细胞系的增殖伴随着 诱导分化。 使用ELISA的免疫和增殖试验，中和 抗体和重组标准品表明至少 一种分泌因子与任何先前表征的细胞因子。 一个因素 具有独特的生物物理和生物化学特性， 通过离子交换、凝胶过滤和疏水过滤的组合纯化， 相互作用色谱目前正在测序。 鉴定来自肿瘤细胞的分泌因子作为免疫调节剂的来源 对淋巴细胞和髓样分化诱导的促有丝分裂活性 支持了这样的观点，即肿瘤免疫环境被 免疫细胞是由可溶性介质定义的，除了良好的- 研究了细胞间的相互作用

This project was aimed at exploring the possible presence of soluble immunoreglatory factors of tumor origin. It was found that the presence of at least four irradiated, cultured human tumor cell lines could stimulate the proliferation of human lymphocytes; the observed proliferative stimulation was due to secreted factors as activity was present in the serum-free tumor cell supernatant (PNAS 87:4058-62, 1990). In addition, this supernatant has now been demonstrated to inhibit the proliferation of three human leukemic cell lines concomitantly with induction of differentiation. Immunologic and proliferative assays using ELLISAs, neutralizing antibodies, and recombinant standards indicated nonidentity of at least one secreted factor with any previously characterized cytokine. A factor with unique biophysical and biochemical properties which has now been purified by a combination of ion exchange, gel filtration, and hydrophobic interaction chromatography is currently being sequenced. Identification of secreted factor(s) from tumor cells as a source of mitogenic activity for lymphocytes and myeloid differentiation induction supports the idea that the tumor immunoenvironment as recognized by immunocytes is defined by soluble mediators in addition to the well- studied cell-cell contact interactions.